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PubMed1991

Ultrastructure of the ciliary process vasculature in cynomolgus monkeys.

The ultrastructure of the ciliary process vasculature in cynomolgus monkeys is described with transmission electron microscopy. Special attention is paid to a special segment of the anterior arterioles (afferent segment) and to the end of the marginal venule (efferent segment)-vascular structures which have been described as haemodynamically important. The major arterial circle of iris (MACI), the exclusive blood supply of the ciliary processes, has only a one- or two-layered medium. A short distance after the anterior arterioles of the ciliary processes have branched off, these arterioles develop a characteristic segment of about 100 microns in length and which possesses a two-layered medium where prominent special myocytes lie on the adventitial side (afferent segment). Nerve endings with dense-core and large vesicles are closely associated to the vessel wall of these afferent segments. On the 'venous' side of the ciliary process vasculature, the very thin wall of the marginal ciliary process vessel becomes reinforced by a layer of myocytes in a segment which is located in the zone where the marginal vessel bends into the layer of the pars plana venules (efferent segment). Here, the endothelium is substantially thickened and filled with different-sized granules. Nerve endings with clear- and large dense-core vesicles lie around this segment.

Animals↗
PubMed1999

The RAG1/RAG2 complex constitutes a 3' flap endonuclease: implications for junctional diversity in V(D)J and transpositional recombination.

During V(D)J recombination, processing of branched coding end intermediates is essential for generating junctional diversity. Here, we report that the RAG1/ RAG2 recombinase is a 3' flap endonuclease. Substrates of this nuclease activity include various coding end intermediates, suggesting a direct role for RAG1/ RAG2 in generating junctional diversity during V(D)J recombination. Evidence is also provided indicating that site-specific RSS nicking involves RAG1/RAG2-mediated processing of a localized flap-like structure, implying 3' flap nicking in multiple DNA processing reactions. We have also demonstrated that the bacterial transposase Tn10 contains a 3' flap endonuclease activity, suggesting a mechanistic parallel between RAG1/RAG2 and other transposases. Based on these data, we propose that numerous transposases may facilitate genomic evolution by removing single-stranded extensions during the processing of excision site junctions.

Animals↗
PubMed1996

Three dimensional anatomy of complete duct systems in human breast: pathological and developmental implications.

AIMS: To reconstruct the arrangement in space of all major ducts and their branches from nipple to periphery of a human breast obtained at necropsy. METHODS: Duct tracing through cleared haematoxylin stained 2 mm sub-gross coronal slices of a complete necropsy breast and computer modelling of duct territories. RESULTS: All branches were traced for 10 complete duct systems of a single breast from a 19 year old girl. Their complexity prevented comprehensive modelling of individual ducts and rami using available computer software, but the territories (catchments) drained by individual duct systems did not overlap and could be reconstructed. Catchment volume and length of the central unbranched duct draining each catchment varied greatly. Duct spacing showed non-random uniformity which is also seen in rodent mammary glands. CONCLUSIONS: These spatial relations are consistent with mutual growth inhibition between duct systems during mammary development. Although there is no clear morphological distinction between mammary duct end buds and lateral buds in women, the present study does suggest that processes of branching morphogenesis occurring during development of the breasts in women do show some analogies with the growth of end buds/lateral branches/alveoli during rodent mammary gland development. Rodent models of mammary development may usefully suggest hypotheses about human breast biology. Less laborious methods of three dimensional reconstruction of mammary ducts and their branches from sub-gross slices, allowing more specimens to be studied, would be valuable for the study of normal human breast development and mammary intraepithelial neoplasia. Increasing power and decreasing costs of high definition image processing hardware and software may make such endeavours practicable.

Adult↗
PubMed1994

Expression of horizontal cell phenotypes in monolayer cultures from immature rabbit retina.

Using the sandwich culture technique introduced by Brewer and Cotman we have studied the in vitro differentiation of A- and B-type horizontal cells which represent two well characterized cell types of the rabbit retina. Neurons from immature (postnatal day 3) rabbit retinae were dissociated and grown on inverted coverslips for up to 5 weeks in a chemically defined medium. On the basis of morphological criteria and the staining pattern for several immunocytochemical and autoradiographic horizontal cell markers we have examined to what extent expression of a distinct mature neuronal phenotype can take place under the artificial conditions of monolayer cultures. After 14 days in vitro neurons could be identified which had acquired elaborate morphological features closely resembling those of A- and B-type horizontal cells, respectively. Axonless A-like cells had 2-4 stout primary dendrites. In agreement with in situ observations these cells showed immunoreactivity for neurofilament proteins (68 kDa, 200 kDa), calbindin-28 kDa and less strongly for vimentin. B-like neurons reached varying states of development. Ideally, they had dendritic trees with 6-8 primary processes extending radially from the soma and a single axon-like process which branched extensively to form a profuse neuritic arbor strikingly similar to axon terminal systems of B-type cells in the intact retina. B-like cells also stained for vimentin, calbindin-28 kDa and unexpectedly also for neurofilament proteins. Interestingly, however, neurofilaments became redistributed during in vitro development eventually resulting in their restricted localization in the 'axon terminal system'. This apparently reflects a developmental process which has escaped detection in situ so far. Both cell types were intensely labelled with antibodies to gamma-aminobutyric acid (GABA), the presumed horizontal cell transmitter, but high affinity uptake of this transmitter was practically undetectable by [3H]-GABA autoradiography. This was in agreement with observations in intact retinae. These results support the notion that once a neuron has reached a certain developmental state further differentiation and maintenance of its particular morphological and functional properties are primarily governed by intrinsic factors, but do not exclude that extrinsic signals have important modulatory functions.

Animals↗
PubMed1996

Amphiregulin in lung branching morphogenesis: interaction with heparan sulfate proteoglycan modulates cell proliferation.

Epithelial and mesenchymal cells isolated from mouse embryonic lungs synthesized and responded to amphiregulin (AR) in a different fashion. Mesenchymal cells produced and deposited 3- to 4-fold more AR than epithelial cells, proliferated in the presence of exogenous AR, and their spontaneous growth was blocked by up to 85% by anti-AR antibodies. In contrast, epithelial cells exhibited a broad response to this growth regulator factor depending on whether they were supplemented with extracellular matrix (ECM) and whether this ECM was of epithelial or mesenchymal origin. AR-treated epithelial cells proliferated by up to 3-fold in the presence of mesenchymal-deposited ECM, remained unchanged in the presence of epithelial-deposited ECM, and decreased in their proliferation rate below controls in the absence of ECM supplementation. This effect was abolished by treatment with the glycosaminoglycan-degrading enzymes heparinase and heparitinase suggesting the specific involvement of heparan sulfate proteoglycan (HSPG) in AR-mediated cell proliferation. In whole lung explants, branching morphogenesis was inhibited by antibodies against the AR heparan sulfate binding site and stimulated by exogenous AR. Since during development, epithelial cells are in contact with mesenchymal ECM at the tips of the growing buds and alongside the basement membrane, focal variations in the proportion of epithelial and mesenchymal HSPG will focally affect epithelial proliferation rates. Therefore, AR-HSPG interaction may underlie the process of branching morphogenesis by inducing differential cell proliferation.

Amphiregulin↗
PubMed1975

Inverse prominence of ependyma and capillaries in the spinal cord of vertebrates: a comparative histochemical study.

Spinal cords of 15 species representing six classes of vertebrates and the protochordate amphioxus were examined with histochemical methods for esterase, ATPase, LDH, PAS, and PAS-phosphorylase. Ependymal and glial cell processes were demonstrated and resembled heavy metal impregnations. Capillaries also were shown. The prominence of glycogen-rich ependymal structures in the spinal cord of nonmammalian vertebrates, and the increase in intramedullary blood vessels in placental mammals, suggest an inverse relationship between the relative development of the ependyma and of the blood supply. The marsupial opossum has sparseness of both ependyma and capillaries, but exhibits an extensive pattern of branched glial processes in both white and gray matter.

Animals↗
PubMed2001

Neuronal properties in cultured ultimobranchial C cells of chick embryos: process outgrowth and expression of TuJ1 and enkephalin.

We have analyzed the neuronal properties in cultured ultimobranchial C cells isolated from embryonic chicks at different developmental stages (12--16 days of incubation) by immunohistochemistry and electron microscopy. The ultimobranchial glands mostly consist of C cell solids. In 13-day-old embryos, many C cells cultured for 7 days on laminin-coated slides extended long neurite-like processes, reaching 300 microm in length. Neuritic outgrowth of C cells was regulated developmentally and virtually unaffected by nerve growth factor (NGF). The cultured C cells expressed intense immunoreactivity for calcitonin and enkephalin. It was also confirmed by confocal laser-scanning microscopy that almost all C cells were intensely immunostained by both the calcitonin antiserum and the monoclonal antibody TuJ1, a neuron-specific marker. Scanning electron microscopy identified the outgrowth of long, branching neuritic processes emerging from C cell soma. The processes had numerous varicosities along their course and ended in growth cones. The C cells with processes were usually monopolar and less frequently bipolar or multipolar. Transmission electron microscopy revealed the presence of membrane-bounded secretory granules in the cultured C cells. The neuritic processes of C cells contained aggregations of microfilaments, intermediate filaments and microtubules arranged in parallel to the long axis. In addition, synaptic-like contacts showing desmosome-like membrane-thickenings and accumulations of small clear vesicles and dense-cored vesicles were formed between the endings of the processes and the surface of C cells. These results indicate that the C cells cultured from early chick embryos (12- and 13-day-old) maintain the neuronal characteristics for long periods in vitro.

Animals↗
PubMed1990

Smooth muscle cell markers in developing rat lung.

We employed a panel of antibodies directed against cytoskeletal and contractile proteins in a developmental study to follow the differentiation and distribution of smooth muscle-like cells in the rat lung. We observed that, in the mesenchyme around developing airways and vessels, desmin replaces vimentin as the predominant intermediate filament as specialization toward smooth muscle occurs. Normally, desmin and smooth muscle myosin were expressed together in the cells and their acquisition appeared indicative of terminal differentiation of smooth muscle. In this regard, the maturation of vascular smooth muscle is delayed in the lung relative to that surrounding the developing air passages. alpha-smooth muscle actin-containing cells form a thicker coat around the primitive airway tubes and extend farther down the tree than desmin or smooth muscle myosin-positive cells. This suggests that the alpha-actin is a marker for initial differentiation of smooth muscle cells and that these cells arise from the enveloping mesenchyme. In the pseudoglandular and canalicular lung, alpha-actin-containing cells were also found in regions of epithelial tube cleft formation, suggesting an association with the process of branching morphogenesis. In addition, a large complement of alpha-actin-positive but smooth muscle myosin-negative cells were observed in the saccular interstitium during the period of secondary saccule formation and capillary reorganization that leads to final alveolarization. In summary, we note an association of smooth muscle-like, alpha-actin-containing cells with areas and periods of remodeling during normal pulmonary development. This observation may have relevance to the repair process in the adult lung.

Actins↗
PubMed1998

Spatial distribution of nerve processes and beta-adrenoreceptors in the rat atrioventricular node.

Atrioventricular (AV) nodal conduction time is known to be modulated by the autonomic nervous system. The presence of numerous parasympathetic and sympathetic nerve fibres in association with conduction tissue in the heart is well authenticated. In this study, confocal microscopy was used to image the distribution of antibodies directed against the general neuronal marker PGP 9.5, tyrosine hydroxylase (TH), vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and beta1 and beta2-adrenoreceptors. Serial 12 microm sections of fresh frozen tissue taken from the frontal plane of the rat atrioventricular node, His bundle and bundle branches were processed for histology, acetylcholinesterase (AChE) activity and immunohistochemistry. It was found that the AV and ventricular conduction systems were more densely innervated than the atrial and ventricular myocardium as revealed by PGP 9.5 immunoreactivity. Furthermore, the transitional cell region was more densely innervated than the midnodal cell region, while spatial distribution of total innervation was uniform throughout all AV nodal regions. AChE-reactive nerve processes were found throughout the AV and ventricular conduction systems, the spatial distribution of which was nonuniform exhibiting a paucity of AChE-reactive nerve processes in the central midnodal cell region and a preponderance in the circumferential transitional cell region. TH-immunoreactivity was uniformly distributed throughout the AV and ventricular conduction systems including the central midnodal and circumferential transitional cell regions. Beta1-adrenoreceptors were found throughout the AV and ventricular conduction systems with a preponderance in the circumferential transitional cell region. Beta2-adrenoreceptors were localised predominantly in AV and ventricular conduction systems with a paucity of expression in the circumferential transitional cell region. These results demonstrate that the overall uniform distribution of total nerve processes is comprised of nonuniformly distributed subpopulations of parasympathetic and sympathetic nerve processes. The observation that the midnodal cell region exhibits a differential spatial pattern of parasympathetic and sympathetic innervation suggests multiple sites for modulation of impulse conduction within this region. Moreover, the localisation of beta2-ARs in the AV conduction system, with an absence of expression in the circumferential transitional cell layer, suggests that subtype-specific pharmacological agents may have distinct effects upon AV nodal conduction.

Acetylcholinesterase↗
PubMed1990

Differentiation of crypt epithelium in human palatine tonsils: the microenvironment of crypt epithelium as a lymphoepithelial organ.

The differentiation of the keratinocytes of the human palatine tonsils were studied by means of light and electron microscopy and immunohistochemistry using a polyclonal (K) and two monoclonal antikeratin antibodies (PKK1, PKK2). In the surface epithelium, the basal cells, cuboidal or columnar in shape, undergo progressive terminal differentiation and are transformed into the flattened cells of the upper layers. K reacts with both the basal and spinous layers, while PKK1 and PKK2 mark exclusively the basal layer. In the neck portion of the crypt, cavities containing one or aggregated lymphocytes with amorphous substances are observed in the spinous layer. The cavities are surrounded by elongated cytoplasmic processes of transformed epithelial cells bearing surface microvilli. These transformed epithelial cells display intense PKK1- and PKK2-positive reactions, whereas other conventional polygonal cells in the vicinity remain PKK1- and PKK2-negative as do those in the surface epithelium. In the deep portion of the crypt, where numerous lymphocytes invade the epithelium, the epithelial cells are transformed into star-shaped reticulum cells showing PKK1- and PKK2-positive reactions. The extended and branched cytoplasmic processes interconnect with one another constituting a complex network of reticulum cells, the well known reticulation of the crypt epithelium. Ten-nm filaments are usually oriented parallel to the longitudinal axis of transformed epithelial cells. Our observations suggest that the cell-shape transformation, i.e., from conventional polygonal epithelial cells into epithelial reticulum cells, occurs when the epithelial cells are in close contact with the infiltrating lymphocytes, and that this transformation is accompanied by a change in keratin phenotype.

Adolescent↗
PubMed2003

Kinetics of random aggregation-fragmentation processes with multiple components.

A computationally efficient algorithm is presented for exact simulation of the stochastic time evolution of spatially homogeneous aggregation-fragmentation processes featuring multiple components or conservation laws. The algorithm can predict the average size and composition distributions of aggregating particles as well as their fluctuations, regardless of the functional form (e.g., composition dependence) of the aggregation or fragmentation kernels. Furthermore, it accurately predicts the complete time evolutions of all moments of the size and composition distributions, even for systems that exhibit gel transitions. We demonstrate the robustness and utility of the algorithm in case studies of linear and branched polymerization processes, the last of which is a two-component process. These simulation results provide the stochastic description of these processes and give new insights into their gel transitions, fluctuations, and long-time behavior when deterministic approaches to aggregation kinetics may not be reliable.

Journal Article↗
PubMed2005

[Transverse radioulnar branch of the dorsal ulnar nerve: anatomic description and arthroscopic implications from 45 cadaveric dissections].

PURPOSE OF THE STUDY: We conducted an anatomic study of the transverse branch of the dorsal ulnar nerve to describe its morphology and position in relation to arthroscopic exploration portals. MATERIAL AND METHODS: Forty-five non-side-matched anatomic specimens of unknown age and gender were preserved in formol. The dorsal branch of the ulnar nerve was identified and dissected proximally to distally in order to reveal the different terminal branches. The morphometric analysis included measurement of the length and diameter of the transverse branch and measurement of wrist width. We also measured the smallest distance between the transverse branch and the ulnar styloid process, and between the branch and usual arthroscopic portals (4-5, 6R, 6U) in the axis of the forearm. RESULTS: The transverse branch was inconstant. It was found in 12 of the 45 dissection specimens (27%). In two-thirds of the specimens, the branch ran over less than 50% of the wrist width, tangentially to the radiocarpal joint. Mean nerve diameter was 1 mm. It was found 5-6 mm from the ulnar styloid process and was distal to it in 83% of the specimens. The dissections demonstrated two anatomic variants. Type A corresponded to a branch running distally to the ulnar styloid process, parallel to the joint line (10/12 specimens). Type B exhibited a trajectory proximal to the ulnar styloid process, crossing the ulnar head (2/12 specimens). The relations with the arthroscopic portals (4-5, 6R, 6U) showed that the mean distance from the branch to the portal was 3.75 mm for the 4-5 portal (distally in 11/12 specimens), 3.68 mm for the 6R portal (distally in 10/12 specimens), and 4.83 mm for the 6U portal (distally in 7 specimens and proximally in 5). DISCUSSION: To our knowledge, there has been only one report specifically devoted to this transverse branch. Two other reports simply mention its existence. According to the literature, the transverse branch of the dorsal ulnar nerve occurs in 60-80% of the cases. We found two anatomic variations different than those described in the literature. Based on our findings and data reported previously, we propose a new classification, describing two main types. In Type 1, the transverse branch arises proximally to the ulnar styloid process;type 1A and type IB are described in relation to the direction of the branch. In Type II, the branch arises distally to the ulnar styloid process;type IIA and type IIB again being described in relation to the direction of the branch. On the tangential trajectory over the radiocarpal joint, the morphometric data show a zone of risk described by a rectangle measuring 10 mm wide (6 mm distal and 4 mm proximal to the ulnar styloid process) and covering 50% of the wrist width. The relations with arthroscopic portals describe a zone of risk corresponding to a 5-7 mm radius circle centered on the portals (4-5, 6R, 6U), which includes 83% of the transverse branches.

Arm↗
PubMed2000

Alteration of gene conversion tract length and associated crossing over during plasmid gap repair in nuclease-deficient strains of Saccharomyces cerevisiae.

A plasmid gap repair assay was used to assess the role of three known nucleases, Exo1, Mre11 and Rad1, in the processing of DNA ends and resolution of recombination intermediates during double-strand gap repair. In this assay, alterations in end processing or branch migration are reflected by the frequency of co-conversion of a chromosomal marker 200 bp from the gap. Gap repair associated with crossing over results in integration at the homologous chromosomal locus, whereas the plasmid remains episomal for non-crossover repair events. In mre11 strains, the frequency of gap repair was reduced 3- to 10-fold and conversion tracts were shorter than in the wild-type strain, consistent with a role for this nuclease in processing double-strand breaks. However, conversion tracts were longer in a strain containing the nuclease deficient allele, mre11-H125N, suggesting increased end processing by redundant nucleases. The frequency of gap repair was reduced 2-fold in rad1 mutants and crossing over was reduced, consistent with a role for Rad1 in cleaving recombination intermediates. The frequency of gap repair was increased in exo1 mutants with a significant increase in crossing over. In exo1 mre11 double mutants gap repair was reduced to below the mre11 single mutant level.

Crossing Over, Genetic↗
PubMed1991

Experimental chemotherapy of Trypanosoma cruzi infection: persistence of parasite antigens and positive serology in parasitologically cured mice.

Mice infected with Trypanosoma cruzi, but parasitologically cured after specific chemotherapy, continued to exhibit positive indirect immunofluorescence serological tests 3-6 months after the therapy. Treatment of trypanosome antigens with monospecific antisera produced in rabbits, and examination by immunoelectron-microscopy following peroxidase labelling disclosed the presence of membrane deposits in cell processes in the spleens of the mice. Similar deposits were observed in the external membranes of T. cruzi amastigotes in the spleens of acutely infected mice, but not in normal control mice. No reaction occurred in tissues not previously treated with the monospecific anti-T. cruzi serum. Positive cells in treated and cured mice, as well as in the not cured or untreated control mice, were located in germinal centres of the splenic white pulp and presented long and branching cytoplasmic processes, which are indicative of dendritic cells of the lymphoid follicles of the spleen.

Animals↗
PubMed2004

Cytoarchitecture of the normal rat olfactory epithelium: light and scanning electron microscopic studies.

The three-dimensional cytoarchitecture of the normal rat olfactory epithelium was examined by scanning electron microscopy (SEM) of KOH digested tissues as well as by light and transmission electron microscopy of plastic sections. Observations specimens from the lateral side of the olfactory epithelium allowed identification of four cell types by their surface structure: olfactory neurons, supporting cells, basal cells, and duct cells of the Bowman's gland. The olfactory neurons were characterized by the presence of a thick apical process (i.e., dendrite) and a thin basal process (i.e., axon). These olfactory neurons tended to be aligned along the vertical axis of the epithelium. Immature olfactory neurons were present at the basal part of the epithelium and had a pear-shaped cell body with a thin and long axon and a short dendrite which failed to reach the epithelial surface. Supporting cells were roughly columnar in shape and occupied the full length of the epithelium. They became thinner in the basal two thirds of their length but had branched foot processes spreading on the basal surface of the epithelium. Basal cells located in the basal epithelial region were oval, round or cuboidal and present among the foot processes of the supporting cells. The ducts of the Bowman's gland entered the epithelium from the lamina propria and took straight, perpendicular courses within the epithelium. These intraepithelial ducts were composed of several slender cells. The acinar cells are sometimes present in the epithelium and appeared as a globular bulge of the duct at the basal part of the epithelium. SEM observation of the basal surface of the olfactory epithelium also clearly showed that axon bundles were surrounded by the sheet-like processes of Schwann cells, the investment being found at the base of the epithelium just before axon bundles leave the epithelium.

Animals↗
PubMed1989

NMDA receptor regulation of neuronal morphology in cultured hippocampal neurons.

The relationship of the activity of specific neurotransmitter receptors to neuronal morphology was studied in cultured dentate granule neurons from embryonic rat hippocampus. These experiments were made possible by the development of a defined serum-free culture medium for growth at densities low enough to observe isolated neurons. N-Methyl-D-aspartate (NMDA) and its specific non-competitive antagonist, MK801, affected neuronal morphology in a reciprocal fashion. Like glutamate, NMDA stimulated extensive branching of neuronal processes. Not only was 75% of the branching blocked by MK801, but the longest process was 250% longer in the presence of MK801. These results suggest that neurotransmitters that act on the NMDA receptor may contribute to development and synaptogenesis.

Animals↗
PubMed1992

Denervation of the motor endplate results in the rapid expression by terminal Schwann cells of the growth-associated protein GAP-43.

Developing and regenerating neurons express high levels of the growth-associated phosphoprotein GAP-43. This membrane protein is not confined to neurons, however, as a number of studies have demonstrated GAP-43 immunoreactivity in central and peripheral glia in vitro and in vivo. We have found that the Schwann cells overlying the terminal motor axon at adult rat skeletal muscle endplates, and the motor axons themselves, are normally not GAP-43 immunoreactive. Within 24 hr of denervation, however, the terminal Schwann cells are positive for a GAP-43 mRNA in situ hybridization signal and are GAP-43 immunoreactive. The immunoreactive GAP-43 cells possess elaborate processes that branch from the endplate region into the perisynaptic zone and stain with defined Schwann cell markers: the calcium binding protein S100 and the low-affinity NGF receptor (NGFr), but not with a fibroblast marker, Thy-1. Reinnervating motor axons are GAP-43 positive, with an appearance quite different from the GAP-43-positive Schwann cells. The reappearance of nerve endings at the motor endplate is followed by the disappearance of GAP-43 labeling in the Schwann cells and of a retraction of their processes. GAP-43 expression in Schwann cells is therefore state dependent, apparently regulated by neural contact. This protein, which is associated in neurons with neurite formation, may participate in the elaboration of processes by Schwann cells when their contact with axons is disrupted.

Animals↗
PubMed1997

Kalirin, a cytosolic protein with spectrin-like and GDP/GTP exchange factor-like domains that interacts with peptidylglycine alpha-amidating monooxygenase, an integral membrane peptide-processing enzyme.

Although the integral membrane proteins that catalyze steps in the biosynthesis of neuroendocrine peptides are known to contain routing information in their cytosolic domains, the proteins recognizing this routing information are not known. Using the yeast two-hybrid system, we previously identified P-CIP10 as a protein interacting with the cytosolic routing determinants of peptidylglycine alpha-amidating monooxygenase (PAM). P-CIP10 is a 217-kDa cytosolic protein with nine spectrin-like repeats and adjacent Dbl homology and pleckstrin homology domains typical of GDP/GTP exchange factors. In the adult rat, expression of P-CIP10 is most prevalent in the brain. Corticotrope tumor cells stably expressing P-CIP10 and PAM produce longer and more highly branched neuritic processes than nontransfected cells or cells expressing only PAM. The turnover of newly synthesized PAM is accelerated in cells co-expressing P-CIP10. P-CIP10 binds to selected members of the Rho subfamily of small GTP binding proteins (Rac1, but not RhoA or Cdc42). P-CIP10 (kalirin), a member of the Dbl family of proteins, may serve as part of a signal transduction system linking the catalytic domains of PAM in the lumen of the secretory pathway to cytosolic factors regulating the cytoskeleton and signal transduction pathways.

Amino Acid Sequence↗