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At least 1,063 records · Page 59Linked to original sources
PubMed2004

Overexpression of glial cell line-derived neurotrophic factor induces genes regulating migration and differentiation of neuronal progenitor cells.

The glial cell line-derived neurotrophic factor (GDNF) is involved in the development and maintenance of neural tissues. Mutations in components of its signaling pathway lead to severe migration deficits of neuronal crest stem cells, tumor formation, or ablation of the urinary system. In animal models of Parkinson's disease, GDNF has been recognized to be neuroprotective and to improve motor function when delivered into the cerebral ventricles or into the substantia nigra. Here, we characterize the network of 43 genes induced by GDNF overproduction of neuronal progenitor cells (ST14A), which mainly regulate migration and differentiation of neuronal progenitor cells. GDNF down-regulates doublecortin, Paf-ah1b (Lis1), dynamin, and alpha-tubulin, which are involved in neocortical lamination and cytoskeletal reorganization. Axonal guidance depends on cell-surface molecules and extracellular matrix proteins. Laminin, Mpl3, Alcam, Bin1, Id1, Id2, Id3, neuregulin1, the ephrinB2-receptor, neuritin, focal adhesion kinase (FAK), Tc10, Pdpk1, clusterin, GTP-cyclooxygenase1, and follistatin are genes up-regulated by GDNF overexpression. Moreover, we found four key enzymes of the cholesterol-synthesis pathway to be down-regulated leading to decreased farnesyl-pyrophospate production. Many proteins are anchored by farnesyl-derivates at the cell membrane. The identification of these GDNF-regulated genes may open new opportunities for directly influencing differentiation and developmental processes of neurons.

Animals↗
PubMed2006

A cell-free biochemical complementation assay reveals complex and redundant cytosolic requirements for LRP endocytosis.

The low density lipoprotein receptor-related protein (LRP) binds multiple, distinct ligands and participates in constitutive endocytosis and signal transduction. Using an in vitro reconstitution system and a new biochemical complementation assay, we have explored the limiting cytosolic requirements for endocytosis of LRP from isolated plasma membranes. We find that clathrin, AP2 and dynamin do not support efficient LRP uptake and that additional factors present in a 30% ammonium sulfate supernatant fraction of bovine brain cytosol (AS supt) are required. Fractionation of the AS supt revealed that multiple and redundant factors are required to support LRP endocytosis. Among these, we identified Hsc70, synaptojanin1 and CRMP-2 by mass spectrometry. Our data suggest that LRP, which bears several distinct endocytic motifs in its cytoplasmic domain, may use multiple pathways for endocytosis in vitro.

Amino Acid Motifs↗
PubMed2003

Mammalian actin binding protein 1 is essential for endocytosis but not lamellipodia formation: functional analysis by RNA interference.

Mammalian actin binding protein 1 (mAbp1, also called SH3P7/Hip55) is structurally and functionally related to yeast Abp1 and to cortactin, both of which have been implicated in endocytotic processes. mAbp1 associates through its SH3 domain with dynamin, a large GTPase essential for vesicle fission. To clarify the function of mAbp1, we specifically knocked down its expression in human embryonic kidney 293T cells, using RNA interference (RNAi). Co-transfection of a short interfering RNA (siRNA) together with a plasmid coding for a surface marker, followed by purification of transfected cells, enabled us to obtain a cell population having up to 90% inhibition of mAbp1 expression. In mAbp1-knocked down cells, transferrin (Tf) receptor endocytosis was significantly inhibited and intracellular distribution of the early endosomal compartment was modified. In contrast, in these cells actin and microtubule filaments appeared normal, and formation of lamellipodia induced by active Rac was not inhibited. This study provides definitive evidence that mAbp1 is indispensable for receptor-mediated endocytosis.

Actin Cytoskeleton↗
PubMed2003

Evaluation of the immortalised mouse brain capillary endothelial cell line, b.End3, as an in vitro blood-brain barrier model for drug uptake and transport studies.

Well-characterised cell lines represent important tools for the study of endogenous solute or xenobiotic transport. A brain microvascular cell line, b.End3, isolated from mice transformed with the Polyoma virus middle T-antigen is available commercially. Here we report the characterisation of some features of b.End3 of relevance to its use in blood-brain barrier transport investigations. The b.End3 cells displayed a distinctive spindle-like squamous morphology in culture. Clathrin coated pits and numerous uncoated intracellular vesicles were evident within the cells, as was the expression of the vesicle-associated proteins, clathrin, caveolin-1, flotillin and dynamin II. In the presence of C6 astroglial co-culture b.End3 monolayers achieved a maximal transendothelial electrical resistance of 130 Omega cm2, but lacked real discrimination with respect to the permeation of transcellular and paracellular probes, e.g. permeability coefficients (x 10(-6) cm s(-1)) for propranolol of approximately 23 vs. 16 for sucrose. RT-PCR analysis confirmed the presence within the b.End3 cells of mRNA transcripts for the following transporters: GLUT-1; MCT 1 and 2; OAT1; Oatp1; mdr 1a and 1b; MRP 1 and 5; beta-alanine, system L and system y+L amino acid carriers; the nucleoside transporters cNT1 and 2, eNT1 and 2, and the tight junctional elements, ZO-1, JAM, occludin, claudin-1 and -5. The b.End3 cells actively accumulated D-glucose in a sodium-independent manner with characteristics consistant with that of GLUT-1. Functionality for P-glycoprotein efflux was evident as assessed by a rhodamine-123 accumulation and retention assay. The system L LAT1/4F2hc amino acid transporter was examined through uptake of L-leucine and L-phenylalanine and provided Km and Vmax values of approximately 16 microM and 350-480 pmol/mg protein/10 min, respectively; the affinity of transport for these substrates being weaker, approximately threefold, when the b.End3 cells were grown in the presence of C6 astroglial factors. Although the b.End3 cells appear unsuitable for transendothelial permeability assessments they display characteristics that would allow their worthwhile use in studies addressing blood-brain barrier transport mechanisms.

Alkaline Phosphatase↗
PubMed2000

Intersectin 2, a new multimodular protein involved in clathrin-mediated endocytosis.

Intersectin 1 (ITSN1) is a binding partner of dynamin that has been shown to participate in clathrin-mediated endocytosis. Here we report the characterization of a new human gene, ITSN2, highly similar to ITSN1. Alternative splicing of ITSN2 generates a short isoform with two EH domains, a coiled-coil region and five SH3 domains, and a longer isoform containing extra carboxy domains (DH, PH and C2 domains), suggesting that it could act as a guanine nucleotide exchange factor for Rho-like GTPases. ITSN2 expression analysis indicates that it is widely expressed in human tissues. Intersectin 2 isoforms show a subcellular distribution similar to other components of the endocytic machinery and co-localize with Eps15. Moreover, their overexpression, as well as the corresponding ITSN1 protein forms, inhibits transferrin internalization.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Isolation of a cDNA for a novel 120-kDa GTP-binding protein expressed in motor neurons in the salmon brain.

We isolated a cDNA encoding a novel protein with GTP-binding motifs from the salmon brain. The cloned 5.5-kb cDNA encoded 971 amino acids, which showed limited homology with members of large GTP-binding proteins, such as dynamin, MX protein and VPS1. By in vitro translation analysis, the size of the encoded protein was estimated to be 120 kDa. The recombinant protein including the putative GTP-binding domain was shown to bind to GTP in vitro. mRNA was strongly expressed in the brain, ovary and skeletal muscle. In the brain, expression of the mRNA was observed specifically in motor neurons, in nucleus oculomotorius, in nucleus valvulae lateralis, in the medulla oblongata and in the spinal cord. To determine the cell biological significance of the encoded protein, we transfected CHO cells with wild type or a putative constitutive active mutant of the mG120 (120-kDa G protein expressed in motor neurons) and examined morphological changes. However, no clear changes were observed. The functional role of this novel motor neuron-specific large GTP-binding protein remains to be elucidated.

Amino Acid Sequence↗
PubMed1999

Molecular events associated with the regulation of signaling by M2 muscarinic receptors.

Multiple events are associated with the regulation of signaling by the M2 muscarinic cholinergic receptors (mAChRs). Desensitization of the attenuation of adenylyl cyclase by the M2 mAChRs appears to involve agonist-dependent phosphorylation of M2 mAChRs by G-protein coupled receptor kinases (GRKs) that phosphorylate the receptors in a serine/threonine rich motif in the 3rd intracellular domain of the receptors. Mutation of residues 307-311 from TVSTS to AVAAA in this domain of the human M2 mAChR results in a loss of receptor/G-protein uncoupling and a loss of arrestin binding. Agonist-induced sequestration of receptors away from their normal membrane environment is also regulated by agonist-induced phosphorylation of the M2 mAChRs on the 3rd intracellular domain, but in HEK cells, the predominant pathway of internalization is not regulated by GRKs or arrestins. This pathway of internalization is not inhibited by a dominant negative dynamin, and does not appear to involve either clathrin coated pits or caveolae. The signaling of the M2 mAChR to G-protein regulated inwardly rectifying K channels (GIRKs) can be modified by RGS proteins. In HEK cells, expression of RGS proteins leads to a constitutive activation of the channels through a mechanism that depends on Gbetagamma. RGS proteins appear to increase the concentration of free Gbetagamma in addition to acting as GAPs. Thus multiple mechanisms acting at either the level of the M2 mAChRs or the G-proteins can contribute to the regulation of signaling via the M2 mAChRs.

Adenylate Cyclase Toxin↗
PubMed2000

mu and delta-opioid receptor agonists induce mitogen-activated protein kinase (MAPK) activation in the absence of receptor internalization.

Agonist-promoted internalization (endocytosis) of G-protein-coupled receptors (GPCRs), including all three opioid receptor types (mu, delta and kappa), has been shown to occur via the clathrin endosomal pathway in response to receptor phosphorylation and the actions of the proteins, beta-arrestin and dynamin. Many members of the GPCR family stimulate mitogen-activated protein kinases (MAPK or ERK) activity and, in several cases, it appears that MAPK activation is dependent on receptor internalization. We have reinvestigated the question of whether internalization is obligatory for MAPK activation by opioid receptors, using cell lines expressing the cloned mu or delta receptor. Morphine, which is known to activate both mu and delta receptors, does not induce their rapid internalization into clathrin-coated endosomes. However, morphine produced a robust stimulation of MAPK in both cell lines, as demonstrated by the appearance of phosphorylated MAPK. Moreover, pre-exposure of cells to the internalization inhibitors, concanavalin A or hypertonic sucrose, totally blocked DAMGO mu-selective agonist) and DTLET (delta-selective agonist)-mediated receptor internalization, yet neither treatment affected MAPK phosphorylation induced by these peptides. Our results provide evidence that receptor internalization is not an obligatory requirement for MAPK activation by mu and delta opioid receptors. Hypotheses are presented to explain the seemingly contradictory results obtained from different laboratories.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2002

Endocytosis and the cytoskeleton.

In this review we describe the potential roles of the actin cytoskeleton in receptor-mediated endocytosis in mammalian cells and summarize the efforts of recent years in establishing a relationship between these two cellular functions. With molecules such as dynamin, syndapin, HIP1R, Abp1, synaptojanin, N-WASP, intersectin, and cortactin a set of molecular links is now available and it is likely that their further characterization will reveal the basic principles of a functional interconnection between the membrane cytoskeleton and the vesicle-budding machinery. We will therefore discuss proteins involved in endocytic clathrin coat formation and accessory factors to control and regulate coated vesicle formation but we will also focus on actin cytoskeletal components such as the Arp2/3 complex, spectrin, profilin, and motor proteins involved in actin dynamics and organization. Additionally, we will discuss how phosphoinositides, such as PI(4,5)P2, small GTPases thought to control the actin cytoskeleton, such as Rho, Rac, and Cdc42, or membrane trafficking, such as Rab GTPases and ARF proteins, and different kinases may participate in the functional connection of actin and endocytosis. We will compare the concepts and different molecular mechanisms involved in mammalian cells with yeast as well as with specialized cells, such as epithelial cells and neurons, because different model organisms often offer complementary advantages for further studies in this thriving field of current cell biological research.

Actins↗
PubMed2006

Cell biology of mitochondrial dynamics.

Mitochondria are the product of an ancient endosymbiotic event between an alpha-proteobacterium and an archael host. An early barrier to overcome in this relationship was the control of the bacterium's proliferation within the host. Undoubtedly, the bacterium (or protomitochondrion) would have used its own cell division apparatus to divide at first and, today a remnant of this system remains in some "ancient" and diverse eukaryotes such as algae and amoebae, the most conserved and widespread of all bacterial division proteins, FtsZ. In many of the eukaryotes that still use FtsZ to constrict the mitochondria from the inside, the mitochondria still resemble bacteria in shape and size. Eukaryotes, however, have a mitochondrial morphology that is often highly fluid, and in their tubular networks of mitochondria, division is clearly complemented by mitochondrial fusion. FtsZ is no longer used by these complex eukaryotes, and may have been replaced by other proteins better suited to sustaining complex mitochondrial networks. Although proteins that divide mitochondria from the inside are just beginning to be characterized in higher eukaryotes, many division proteins are known to act on the outside of the organelle. The most widespread of these are the dynamin-like proteins, which appear to have been recruited very early in the evolution of mitochondria. The essential nature of mitochondria dictates that their loss is intolerable to human cells, and that mutations disrupting mitochondrial division are more likely to be fatal than result in disease. To date, only one disease (Charcot-Marie-Tooth disease 2A) has been mapped to a gene that is required for mitochondrial division, whereas two other diseases can be attributed to mutations in mitochondrial fusion genes. Apart from playing a role in regulating the morphology, which might be important for efficient ATP production, research has indicated that the mitochondrial division and fusion proteins can also be important during apoptosis; mitochondrial fragmentation is an early triggering (and under many stimuli, essential) step in the pathway to cell suicide.

Animals↗
PubMed2005

Nucleotide binding and self-stimulated GTPase activity of human guanylate-binding protein 1 (hGBP1).

The synthesis of human guanylate-binding protein 1 (hGBP1) is induced by interferon-gamma and its biological function is related to antiviral activity and regulation of proliferation. It interacts with guanine nucleotides, and its catalytic activity on GTP hydrolysis leads to the formation of phosphate ions and both GDP and GMP. Similar to other large GTPases like dynamin, hGBP1 shows higher specific GTP hydrolysis activity with increasing concentration of the protein. This is based on nucleotide-dependent self-association of hGBP1, which leads to self-stimulation of its GTPase activity. In this chapter we describe the characterization of the basic biochemical properties of hGBP1. Essentially, the biological activity of a GTPase is controlled by the type of nucleotide bound. Therefore, nucleotide binding is quantified in terms of affinity and dynamics since both of these aspects are important for the occurrence of hGBP1 bound to the one or the other nucleotide. In addition, we analyze the self-stimulated GTPase activity and show how to extract the hGBP1 homodimer dissociation constant from these data. Finally, with the help of size exclusion chromatography, nucleotide-dependent formation of hGBP1 dimers and tetramers is demonstrated. These biochemical characteristics may help to further understand the biological function of hGBP1.

Chromatography, Gel↗
PubMed2000

Cloning and analysis of expression of Mx cDNA in Japanese flounder, Paralichthys olivaceus.

Myxovirus resistance (Mx) is an interferon (IFN)-induced protein that specifically prevents growth, in vivo and in vitro, of certain classes of virus. We isolated the Mx cDNA from a leukocyte cDNA library obtained from a Japanese flounder infected with Hirame rhabdovirus (HRV). The Mx cDNA was found to contain 2385 bp coding for 620 amino acids. The amino acid sequence had approximately 51 and 78% identities to the sequences of human and rainbow trout Mx cDNAs, respectively. We propose that the amino acid sequence encoded by this cDNA clone contains a tripartite guanosine-5'-triphosphate (GTP)-binding motif, GXXXSGKS/T, DXXG and T/NKXD, and a signature of the dynamin family, LPRG(S/K)GIVTR, which are conserved in all IFN-induced Mx proteins of vertebrates. In addition, the C-terminal region of the Japanese flounder Mx protein, like those of other Mx proteins, contains a highly conserved leucine zipper motif. Japanese flounder infected with the HRV showed increased expression of Mx mRNA in the leukocytes starting at 48 h and peaking at 72 h. An RT-PCR (reverse transcription-polymerase chain-reaction) analysis of Mx mRNA from a healthy fish showed that the Mx mRNA was predominantly expressed in the kidney, spleen, intestine, brain, peritoneal cavity fluid and gill, and only minimally expressed in leukocytes, liver, muscle and mucus.

Amino Acid Sequence↗
PubMed2003

Mitochondrial membrane fusion.

Mitochondrial fusion has been observed in a great variety of organisms from yeast to man. It serves to mix and unify the mitochondrial compartment and plays roles in cellular aging, cell development, energy dissipation and mitochondrial DNA inheritance. Large GTPases in the mitochondrial outer membrane, termed Fzo or mitofusins, have been identified as key components of the mitochondrial fusion machinery in yeast, flies and mammalian cells. Recent studies in yeast suggest an involvement of a dynamin-related protein in the intermembrane space. Additional components have been identified by genetic screens. These findings suggest a unique and evolutionarily conserved mechanism for mitochondrial membrane fusion.

Animals↗
PubMed2003

Regional and developmental regulation of syntaphilin expression in the brain: a candidate molecular element of synaptic functional differentiation.

The conserved nature of the basic machinery underlying synaptic function makes it necessary to search for other factors--structural and molecular--that could account for the tremendous diversity found among synapses even within a single neuron. Syntaphilin is a presynaptic membrane protein previously described as a molecular clamp that controls free syntaxin-1A and dynamin-1 availability, and thereby regulates synaptic vesicle exocytosis and endocytosis at the nerve terminal. In this study, we report our finding that syntaphilin expression is developmentally regulated, and show that syntaphilin is expressed most prominently in the mature rat brain, in areas that have been previously characterized to undergo synaptic plastic change. We also find that syntaphilin undergoes divergent subcellular targeting to the mitochondrial outer membrane and the synaptic plasma membrane, giving rise to two neuronal subpopulations of the protein that are modified in their relative enrichment with synaptic maturation and with the formation of cell contacts. Finally, we demonstrate that syntaphilin expression is initiated with induction of neuronal differentiation in PC12 cells. Given its biochemical and functional properties, the spatially and temporally limited nature of syntaphilin expression provides evidence that syntaphilin could be a molecular element of synaptic functional differentiation.

Animals↗
PubMed2001

Caveolae: from basic trafficking mechanisms to targeting transcytosis for tissue-specific drug and gene delivery in vivo.

Continuous endothelium and epithelium create formidable barriers to endogenous molecules as well as targeted drug and gene therapies in vivo. Caveolae represent a possible vesicular trafficking pathway through cell barriers. Here we discuss recent discoveries regarding the basic function of caveolae in transport including transcellular trafficking, intracellular trafficking to distinct endosomes, and molecular mechanisms mediating their budding, docking and fusion (dynamin and SNARE machinery). New technologies to purify and map caveolae as well as generate new probes selectively targeting caveolae in vivo provide valuable tools not only for investigating caveolar endocytosis/transcytosis but also elucidating new potential applications for site-directed treatment of many diseases. Vascular targeting of the caveolar trafficking pathway may be a useful strategy for achieving tissue-specific pharmacodelivery that also overcomes key, normally restrictive cell barriers which greatly reduce the efficacy of many therapies in vivo.

Animals↗
PubMedDate not supplied

Intracellular signaling pathways mediated by the gonadotropin-releasing hormone (GnRH) receptor.

The hypothalamic gonadotropin-releasing hormone (GnRH) is a key regulator of the reproductive system, triggering the synthesis and release of LH and FSH in the pituitary. GnRH transmits its signal via two specific serpentine receptors that belong to the large group of G-protein coupled receptors (GPCRs). Here we review the intracellular signaling pathways mediated by the GnRH receptor (GnRHR). In pituitary-derived alpha T3-1 cells, a widely used model for GnRH action, GnRHR signaling includes activation of mitogen-activated protein kinase (MAPK) cascades, which provide an important link for the transmission of signals from the cell surface to the nucleus and play a role in the regulation of gonadotropin transcription. Activation of ERK--one of the MAPK cascades--by GnRH in these cells depends mainly on the phosphorylation of Raf1 by PKC, supported by a pathway involving c-Src, dynamin, and Ras. On the other hand, the activation of JNK, another MAPK cascade, involves PKC, c-Src, CDC42/Rac1, and probably MEKK1. The GnRHR is also expressed in non-pituitary cells and was found to be involved in the inhibition of cell proliferation in certain cells. Therefore, GnRHR represents a potential target for GnRH-analogs used for cancer treatment. Interestingly, the signaling mechanism of the GnRHR in other cell types significantly differs from that in pituitary cells. Studies conducted in GnRHR-expressing COS7 cells have shown that GnRHR transmits its signals mainly via Gi, EGF receptor, c-Src, and is not dependent on PKC. Understanding the signaling mechanisms elicited by GnRHR can shed light on the mechanism of action of GnRH in pituitary and extra-pituitary tissues.

Animals↗
PubMed2002

Mechanisms of metabotropic glutamate receptor desensitization: role in the patterning of effector enzyme activation.

Metabotropic glutamate receptors (mGluRs) constitute an unique subclass of G protein-coupled receptors (GPCRs). These receptors are activated by the excitatory amino acid glutamate and play an essential role in regulating neural development and plasticity. In the present review, we overview the current understanding regarding the molecular mechanisms involved in the desensitization and endocytosis of Group 1 mGluRs as well as the relative contribution of desensitization to the spatial-temporal patterning of glutamate receptor signaling. Similar to what has been reported previously for prototypic GPCRs, mGluRs desensitization is mediated by second messenger-dependent protein kinases and GPCR kinases (GRKs). However, it remains to be determined whether mGluRs phosphorylation by GRKs and beta-arrestin binding are absolutely required for desensitization. Group 1 mGluRs endocytosis is both agonist-dependent and -independent. Agonist-dependent mGluRs internalization is mediated by a beta-arrestin- and dynamin-dependent clathrin-coated vesicle dependent endocytic pathway. The activation of Group 1 mGluRs also results in oscillatory Gq protein-coupling leading to the cyclical activation of phospholipase Cbeta thereby stimulating oscillations in both inositol 1,4,5-triphosphate formation and Ca(2+) release from intracellular stores. These glutamate receptor-stimulated Ca(2+) oscillations are translated into the synchronous activation of protein kinase C (PKC), which has led to the hypothesis that oscillatory mGluRs signaling involves the repetitive phosphorylation of mGluRs by PKC. However, recent experimental evidence suggests that oscillatory signaling is an intrinsic glutamate receptor property that is independent of feedback receptor phosphorylation by PKC. The challenge in the future will be to determine the structural determinants underlying mGluRs-mediated spatial-temporal signaling as well as to understand how complex signaling patterns can be interpreted by cells in both the developing and adult nervous systems.

Animals↗
PubMed1999

Immunohistochemical distribution of the prohormone convertase PC5-A in rat brain.

Prohormone convertase 5 is an endoprotease of the kexin/subtilisin-like family, which has been postulated to play a role in the proteolytic maturation of a variety of pro-peptides in the mammalian brain. In order to gain insight into the functional role of prohormone convertase 5 in the central nervous system, the regional, cellular and subcellular distributions of the enzyme were investigated by immunohistochemistry in rat brain using an N-terminal-directed specific antibody shown previously to recognize both the mature and unprocessed forms of the enzyme. Throughout the brain, prohormone convertase 5 immunoreactivity was concentrated within nerve cell bodies and proximal dendrites. No prohormone convertase 5 immunoreactivity was associated with astrocytes, as confirmed by the absence of prohormone convertase 5 immunolabeling in cells immunopositive for the glial protein S-100alpha. Within neurons, prohormone convertase 5 immunoreactivity was concentrated within the Golgi apparatus, as revealed immunohistochemically within the same sections using antibodies against the medial cisternae protein MG-160. It was also present within small vesicular-like elements distributed throughout the cytoplasm of perikarya and dendrites, but not of axons, as confirmed by its lack of co-localization with the synaptic terminal marker Dynamin-1. These results suggest that prohormone convertase 5 is active within early compartments of the neuronal regulated secretory pathway and that it is unlikely to be released with its processed substrates. At the regional level, prohormone convertase 5-immunoreactive perikarya were distributed extensively throughout the forebrain. The most numerous and intensely labeled were detected in the olfactory bulb, cerebral cortex, globus pallidus, endopeduncular and subthalamic nuclei, septum, diagonal band of Broca, magnocellular and medial preoptic areas, supraoptic and arcuate nuclei of the hypothalamus, and anterodorsal, laterodorsal, paraventricular and reticular nuclei of the thalamus. Moderate to dense neuronal labeling was also evident in the olfactory tubercle, caudate-putamen, claustrum, bed nucleus of the stria terminalis, substantia innominata, hippocampus, amygdala, and remaining thalamic and hypothalamic nuclei. This widespread distribution suggests that prohormone convertase 5 is involved in the processing of a variety of neuropeptide and/or neurotrophin precursors in mammalian brain.

Animals↗