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Ulrich Tepass

Publications and source records attributed to Ulrich Tepass.

At least 19 recordsLinked to original sources
PubMed2006

Adherens junctions in Drosophila retinal morphogenesis.

Adherens junctions and their core molecular components, classic cadherins, make major contributions to animal morphogenesis. Although the significance of cadherins in development is generally accepted, the mechanisms regulating adherens junction function during morphogenesis remain a subject of intense research. Adherens junctions are involved in the organization of simple cellular patterns, and more complex cell shape changes and cell movements that depend on the dynamic modulation of adherens junctions.

Actins↗
PubMed2006

The FERM protein Yurt is a negative regulatory component of the Crumbs complex that controls epithelial polarity and apical membrane size.

The Crumbs (Crb) complex is a key regulator of epithelial cell architecture where it promotes apical membrane formation. Here, we show that binding of the FERM protein Yurt to the cytoplasmic domain of Crb is part of a negative-feedback loop that regulates Crb activity. Yurt is predominantly a basolateral protein but is recruited by Crb to apical membranes late during epithelial development. Loss of Yurt causes an expansion of the apical membrane in embryonic epithelia and photoreceptor cells similar to Crb overexpression and in contrast to loss of Crb. Analysis of yurt crb double mutants suggests that these genes function in one pathway and that yurt negatively regulates crb. We also show that the mammalian Yurt orthologs YMO1 and EHM2 bind to mammalian Crb proteins. We propose that Yurt is part of an evolutionary conserved negative-feedback mechanism that restricts Crb complex activity in promoting apical membrane formation.

Animals↗
PubMed2006

The agrin/perlecan-related protein eyes shut is essential for epithelial lumen formation in the Drosophila retina.

The formation of epithelial lumina is a fundamental process in animal development. Each ommatidium of the Drosophila retina forms an epithelial lumen, the interrhabdomeral space, which has a critical function in vision as it optically isolates individual photoreceptor cells. Ommatidia containing an interrhabdomeral space have evolved from ancestral insect eyes that lack this lumen, as seen, for example, in bees. In a genetic screen, we identified eyes shut (eys) as a gene that is essential for the formation of matrix-filled interrhabdomeral space. Eys is closely related to the proteoglycans agrin and perlecan and secreted by photoreceptor cells into the interrhabdomeral space. The honeybee ortholog of eys is not expressed in photoreceptors, raising the possibility that recruitment of eys expression has made an important contribution to insect eye evolution. Our findings show that the secretion of a proteoglycan into the apical matrix is critical for the formation of epithelial lumina in the fly retina.

Agrin↗
PubMed2005

Drosophila melanogaster Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli.

Actin-based protrusions can form prominent structures on the apical surface of epithelial cells, such as microvilli. Several cytoplasmic factors have been identified that control the dynamics of actin filaments in microvilli. However, it remains unclear whether the plasma membrane participates actively in microvillus formation. In this paper, we analyze the function of Drosophila melanogaster cadherin Cad99C in the microvilli of ovarian follicle cells. Cad99C contributes to eggshell formation and female fertility and is expressed in follicle cells, which produce the eggshells. Cad99C specifically localizes to apical microvilli. Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length. Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain-binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length. This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.

Animals↗
PubMed2005

Essential function of Drosophila Sec6 in apical exocytosis of epithelial photoreceptor cells.

Polarized exocytosis plays a major role in development and cell differentiation but the mechanisms that target exocytosis to specific membrane domains in animal cells are still poorly understood. We characterized Drosophila Sec6, a component of the exocyst complex that is believed to tether secretory vesicles to specific plasma membrane sites. sec6 mutations cause cell lethality and disrupt plasma membrane growth. In developing photoreceptor cells (PRCs), Sec6 but not Sec5 or Sec8 shows accumulation at adherens junctions. In late PRCs, Sec6, Sec5, and Sec8 colocalize at the rhabdomere, the light sensing subdomain of the apical membrane. PRCs with reduced Sec6 function accumulate secretory vesicles and fail to transport proteins to the rhabdomere, but show normal localization of proteins to the apical stalk membrane and the basolateral membrane. Furthermore, we show that Rab11 forms a complex with Sec5 and that Sec5 interacts with Sec6 suggesting that the exocyst is a Rab11 effector that facilitates protein transport to the apical rhabdomere in Drosophila PRCs.

Adherens Junctions↗
PubMed2005

Mutations in Drosophila sec15 reveal a function in neuronal targeting for a subset of exocyst components.

The exocyst is a complex of proteins originally identified in yeast that has been implicated in polarized secretion. Components of the exocyst have been implicated in neurite outgrowth, cell polarity, and cell viability. We have isolated an exocyst component, sec15, in a screen for genes required for synaptic specificity. Loss of sec15 causes a targeting defect of photoreceptors that coincides with mislocalization of specific cell adhesion and signaling molecules. Additionally, sec15 mutant neurons fail to localize other exocyst members like Sec5 and Sec8, but not Sec6, to neuronal terminals. However, loss of sec15 does not cause cell lethality in contrast to loss of sec5 or sec6. Our data suggest a role of Sec15 in an exocyst-like subcomplex for the targeting and subcellular distribution of specific proteins. The data also show that functions of other exocyst components persist in the absence of sec15, suggesting that different exocyst components have separable functions.

Amino Acid Sequence↗
PubMed2004

Function of Rho GTPases in embryonic blood cell migration in Drosophila.

Hemocyte development in the Drosophila embryo is a genetic model to study blood cell differentiation, cell migration and phagocytosis. Macrophages, which make up the majority of embryonic hemocytes, migrate extensively as individual cells on basement membrane-covered surfaces. The molecular mechanisms that contribute to this migration process are currently not well understood. We report the generation, by P element replacement, of two Gal4 lines that drive expression of UAS-controlled target genes during early (gcm-Gal4) or late (Coll-Gal4) stages of macrophage migration. gcm-Gal4 is used for live imaging analysis showing that macrophages extend large, dynamic lamellipodia as their main protrusions as well as filopodia. We use both Gal4 lines to express dominantnegative and constitutively active isoforms of the Rho GTPases Rac1, Cdc42, Rho1 and RhoL in macrophages, and complement these experiments by analyzing embryos mutant for Rho GTPases. Our findings suggest that Rac1 and Rac2 act redundantly in controlling migration and lamellipodia formation in Drosophila macrophages, and that the third Drosophila Rac gene, Mtl, makes no significant contribution to macrophage migration. Cdc42 appears not to be required within macrophages but in other tissues of the embryo to guide macrophages to the ventral trunk region. No evidence was found for a requirement of Rho1 or RhoL in macrophage migration. Finally, to estimate the number of genes whose zygotic expression is required for macrophage migration we analyzed 208 chromosomal deletions that cover most of the Drosophila genome. We find eight deletions that cause defects in macrophage migration suggesting the existence of approximately ten zygotic genes essential for macrophage migration.

Animals↗
PubMed2004

The cell fate determinant numb interacts with EHD/Rme-1 family proteins and has a role in endocytic recycling.

The adaptor protein Numb is necessary for the cell fate specification of progenitor cells in the Drosophila nervous system. Numb is evolutionarily conserved and previous studies have provided evidence for a similar functional role during mammalian development. The Numb protein has multiple protein-protein interaction regions including a phosphotyrosine binding (PTB) domain and a carboxy-terminal domain that contains conserved interaction motifs including an EH (Eps15 Homology) domain binding motif and alpha-adaptin binding site. In this study we identify the EHD/Rme-1/Pincher family of endocytic proteins as Numb interacting partners in mammals and Drosophila. The EHD/Rme-1 proteins function in recycling of plasma membrane receptors internalized by both clathrin-mediated endocytosis and a clathrin-independent pathway regulated by ADP ribosylation factor 6 (Arf6). Here we report that Numb colocalizes with endogenous EHD4/Pincher and Arf6 and that Arf6 mutants alter Numb subcellular localization. In addition, we present evidence that Numb has a novel function in endosomal recycling and intracellular trafficking of receptors.

ADP-Ribosylation Factor 6↗
PubMed2004

Sinuous is a Drosophila claudin required for septate junction organization and epithelial tube size control.

Epithelial tubes of the correct size and shape are vital for the function of the lungs, kidneys, and vascular system, yet little is known about epithelial tube size regulation. Mutations in the Drosophila gene sinuous have previously been shown to cause tracheal tubes to be elongated and have diameter increases. Our genetic analysis using a sinuous null mutation suggests that sinuous functions in the same pathway as the septate junction genes neurexin and scribble, but that nervana 2, convoluted, varicose, and cystic have functions not shared by sinuous. Our molecular analyses reveal that sinuous encodes a claudin that localizes to septate junctions and is required for septate junction organization and paracellular barrier function. These results provide important evidence that the paracellular barriers formed by arthropod septate junctions and vertebrate tight junctions have a common molecular basis despite their otherwise different molecular compositions, morphologies, and subcellular localizations.

Animals↗
PubMed2003

Organogenesis: keeping in touch with the germ cells.

DE-cadherin and its novel regulator, the transmembrane protein Fear of Intimacy, have been found to control the adhesive interactions between germline and somatic cells that lead to gonad formation in Drosophila.

Animals↗
PubMed2003

CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina.

Mutations within the CRB1 gene have been shown to cause human retinal diseases including retinitis pigmentosa and Leber congenital amaurosis. We have recently identified a mouse model, retinal degeneration 8 (rd8) with a single base deletion in the Crb1 gene. This mutation is predicted to cause a frame shift and premature stop codon which truncates the transmembrane and cytoplasmic domain of CRB1. Like in Drosophila crumbs (crb) mutants, staining for adherens junction proteins known to localize to the external limiting membrane, the equivalent of the zonula adherens in the mammalian retina, is discontinuous and fragmented. Shortened photoreceptor inner and outer segments are observed as early as 2 weeks after birth, suggesting a developmental defect in these structures rather than a degenerative process. Photoreceptor degeneration is observed only within regions of retinal spotting, which is seen predominantly in the inferior nasal quadrant of the eye, and is caused by retinal folds and pseudorosettes. Photoreceptor dysplasia and degeneration in Crb1 mutants strongly vary with genetic background, suggesting that the variability in phenotypes of human patients that carry mutations in CRB1 may be due to interactions with background modifiers in addition to allelic variations. The Crb1rd8 mouse model will facilitate the analysis of Crb1 function in the neural retina and the identification of interacting factors as candidate retinal disease genes.

Alternative Splicing↗
PubMed2003

Gliotactin, a novel marker of tricellular junctions, is necessary for septate junction development in Drosophila.

Septate junctions (SJs), similar to tight junctions, function as transepithelial permeability barriers. Gliotactin (Gli) is a cholinesterase-like molecule that is necessary for blood-nerve barrier integrity, and may, therefore, contribute to SJ development or function. To address this hypothesis, we analyzed Gli expression and the Gli mutant phenotype in Drosophila epithelia. In Gli mutants, localization of SJ markers neurexin-IV, discs large, and coracle are disrupted. Furthermore, SJ barrier function is lost as determined by dye permeability assays. These data suggest that Gli is necessary for SJ formation. Surprisingly, Gli distribution only colocalizes with other SJ markers at tricellular junctions, suggesting that Gli has a unique function in SJ development. Ultrastructural analysis of Gli mutants supports this notion. In contrast to other SJ mutants in which septa are missing, septa are present in Gli mutants, but the junction has an immature morphology. We propose a model, whereby Gli acts at tricellular junctions to bind, anchor, or compact SJ strands apically during SJ development.

Animals↗
PubMed2003

Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization.

Several protein complexes that are involved in epithelial apicobasal polarity have been identified. However, the mechanism by which these complexes interact to form an integrated polarized cell morphology remains unclear. Crumbs (Crb) and Lethal giant larvae (Lgl) are components of distinct complexes that regulate epithelial polarization in Drosophila melanogaster, but may not interact directly as they localize to the apical and basolateral membrane, respectively. Nevertheless, a genetic screen identifies marked functional interactions between crb and lgl. These interactions extend to other genes within the crb (stardust, sdt) and lgl (discs large, dlg; scribble, scrib) pathways. Our findings suggest that the crb and lgl pathways function competitively to define apical and basolateral surfaces. They also suggest that in the absence of lgl pathway activity, the crb pathway is not required to maintain epithelial polarity. Moreover, we show that crb and lgl cooperate in zonula adherens formation early in development. At later stages, epithelial cells in these mutants acquire normal polarity, indicating the presence of compensatory mechanisms. We find that bazooka (baz) functions redundantly with crb/sdt to support apical polarity at mid- to late-embryogenesis. Despite regaining cell polarity, however, epithelial cells in crb and lgl pathway mutants fail to re-establish normal overall tissue architecture, indicating that the timely acquisition of polarized cell structure is essential for normal tissue organization.

Animals↗
PubMed2002

Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis.

The apical transmembrane protein Crumbs is a central regulator of epithelial apical-basal polarity in Drosophila. Loss-of-function mutations in the human homologue of Crumbs, CRB1 (RP12), cause recessive retinal dystrophies, including retinitis pigmentosa. Here we show that Crumbs and CRB1 localize to corresponding subdomains of the photoreceptor apical plasma membrane: the stalk of the Drosophila photoreceptor and the inner segment of mammalian photoreceptors. These subdomains support the morphogenesis and orientation of the photosensitive membrane organelles: rhabdomeres and outer segments, respectively. Drosophila Crumbs is required to maintain zonula adherens integrity during the rapid apical membrane expansion that builds the rhabdomere. Crumbs also regulates stalk development by stabilizing the membrane-associated spectrin cytoskeleton, a function mechanistically distinct from its role in epithelial apical-basal polarity. We propose that Crumbs is a central component of a molecular scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain. Defects in such scaffolds may contribute to human CRB1-related retinal dystrophies.

Adherens Junctions↗
PubMed2002

Adherens junctions: new insight into assembly, modulation and function.

Adherens junctions play pivotal roles in cell and tissue organization and patterning by mediating cell adhesion and cell signaling. These junctions consist of large multiprotein complexes that join the actin cytoskeleton to the plasma membrane to form adhesive contacts between cells or between cells and extracellular matrix. The best-known adherens junction is the zonula adherens (ZA) that forms a belt surrounding the apical pole of epithelial cells. Recent studies in Drosophila have further illuminated the structure of adherens junctions. Scaffolding proteins encoded by the stardust gene are novel components of the Crumbs complex, which plays a critical role in ZA assembly.1-3 The small GTPase Rap1 controls the symmetric re-assembly of the ZA after cell division.4 Finally, the asymmetric distribution of adherens junction material regulates spindle orientation during asymmetric cell division in the sensory organ lineage.

Adherens Junctions↗