<i>Drosophila melanogaster</i> Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli

D'Alterio, Cecilia; Tran, Dao D.D.; Yeung, Maggie W.Y. Au; Hwang, Michael S.; Li, Michelle A.; Arana, Claudia J.; Mulligan, Vikram Khipple; Kubesh, Mary; Sharma, Praveer P.; Chase, Maretta; Tepaß, Ulrich; Godt, Dorothea

doi:10.1083/jcb.200507072

Cited by 76 publications

(104 citation statements)

References 59 publications

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“…Likewise, transfection of PA2.26 antigen, a plasma membrane glycoprotein with mucin type oligosaccharides, creates filopodia and ruffles (50). Furthermore, high expression of a cadherin homologue without an intracellular domain to bind cytoskeleton still increases microvillus length (8). Cell surface glycoconjugates or bulky membrane molecules other than hyaluronan may thus also have these control and support functions on plasma membrane protrusions.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that there is a strong intrinsic potential in cells to display these extensions, ready for implementation by factors even outside the effector and signaling chains directly related to actin. Indeed, at the molecular level, mechanisms that induce the growth of microvilli in vivo are still somewhat obscure (8). We present a novel factor, active hyaluronan synthesis, apparently unrelated to any of the previously described signaling or actin polymerization processes, that triggers extensive microvillus formation in several cell types.…”

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confidence: 99%

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Hyaluronan Synthesis Induces Microvillus-like Cell Surface Protrusions

Kultti

Rilla

Tiihonen

et al. 2006

Journal of Biological Chemistry

121

134

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Hyaluronan synthases (HASs) are plasma membrane enzymes that simultaneously elongate, bind, and extrude the growing hyaluronan chain directly into extracellular space. In cells transfected with green fluorescent protein (GFP)-tagged Has3, the dorsal surface was decorated by up to 150 slender, 3-20-m-long microvillus-type plasma membrane protrusions, which also contained filamentous actin, the hyaluronan receptor CD44, and lipid raft microdomains. Enzymatic activity of HAS was required for the growth of the microvilli, which were not present in cells transfected with other GFP proteins or inactive GFP-Has3 mutants or in cells incubated with exogenous soluble hyaluronan. The microvilli induced by HAS3 were gradually withered by introduction of an inhibitor of hyaluronan synthesis and rapidly retracted by hyaluronidase digestion, whereas they were not affected by competition with hyaluronan oligosaccharides and disruption of the CD44 gene, suggesting independence of hyaluronan receptors. The data bring out the novel concept that the glycocalyx created by dense arrays of hyaluronan chains, tethered to HAS during biosynthesis, can induce and maintain prominent microvilli.Vertebrate cells display slender plasma membrane protrusions like filopodia, microspikes, and microvilli, the formation and maintenance of which are thought to depend on the dynamics of a bundle of actin filaments in the core of these extensions (1). In selected environments, most of the components in the actin polymerization apparatus, when overexpressed or experimentally activated, have been reported to increase the growth of filopodia or microvilli (2-7). This suggests that there is a strong intrinsic potential in cells to display these extensions, ready for implementation by factors even outside the effector and signaling chains directly related to actin. Indeed, at the molecular level, mechanisms that induce the growth of microvilli in vivo are still somewhat obscure (8). We present a novel factor, active hyaluronan synthesis, apparently unrelated to any of the previously described signaling or actin polymerization processes, that triggers extensive microvillus formation in several cell types. Interestingly, the process is primarily driven by the cell surface glycocalyx rather than intracellular systems.Hyaluronan is an ubiquitous pericellular and extracellular matrix glycosaminoglycan important in embryonic development (9), wound healing (10), inflammation (11, 12), mammalian fertilization (13), and cancer (14). It is involved in cell adhesion (15), migration (16 -19), proliferation and epithelial-mesenchymal transition (9), resistance to apoptosis, and multidrug resistance (14). Some of its effects are thought to be mediated by an ability to form a hydrated pericellular matrix, a coat that can modify cellular interactions with other matrix components and neighboring cells, directly regulating processes such as differentiation and migration (20). Some of the biological signals elicited by hyaluronan are dependent on its CD44 receptor on cell su...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Hyaluronan Synthesis Induces Microvillus-like Cell Surface Protrusions

Kultti

Rilla

Tiihonen

et al. 2006

Journal of Biological Chemistry

121

134

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“…Cadherin-23 is expressed in developing hair bundles at centrosomes and along the stereocilia, and is required for mechanotransduction Sollner et al 2004;Lagziel et al 2005), but its function is not yet clear. A Drosophila ortholog of Pcdh15, Cad99C, regulates the length of apical microvilli in ovarian follicle cells (D'Alterio et al 2005). These studies highlight roles for a variety of cadherin subtypes in the complex organization of stereocilia, and it will be interesting to learn how their activities are coordinated and function in intercellular pathways.…”

Section: Atypical Cadherins In Vertebrate Developmentmentioning

confidence: 99%

Cadherins in development: cell adhesion, sorting, and tissue morphogenesis

Halbleib¹,

Nelson²

2006

Genes Dev.

932

861

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Tissue morphogenesis during development is dependent on activities of the cadherin family of cell-cell adhesion proteins that includes classical cadherins, protocadherins, and atypical cadherins (Fat, Dachsous, and Flamingo). The extracellular domain of cadherins contains characteristic repeats that regulate homophilic and heterophilic interactions during adhesion and cell sorting. Although cadherins may have originated to facilitate mechanical cell-cell adhesion, they have evolved to function in many other aspects of morphogenesis. These additional roles rely on cadherin interactions with a wide range of binding partners that modify their expression and adhesion activity by local regulation of the actin cytoskeleton and diverse signaling pathways. Here we examine how different members of the cadherin family act in different developmental contexts, and discuss the mechanisms involved.Cadherins were originally identified as cell surface glycoproteins responsible for Ca 2+ -dependent homophilic cell-cell adhesion during morula compaction in the preimplantation mouse embryo and during chick development (Yoshida and Takeichi 1982;Gallin et al. 1983;Peyrieras et al. 1983). Subsequently, >100 family members have been identified with diverse protein structures, but all with characteristic extracellular cadherin repeats (ECs) (Nollet et al. 2000). Cadherins are important in both simple and complex organisms. In addition to vertebrates, insects, and nematodes, members of the cadherin family are found in unicellular choanoflagellates (King et al. 2003), the diploblast Hydra (Hobmayer et al. 2000), and the sponge Oscarella carmela (Nichols et al. 2006).In the three decades since their discovery, it has become clear that the role of cadherins is not limited to mechanical adhesion between cells. Rather, cadherin function extends to multiple aspects of tissue morphogenesis, including cell recognition and sorting, boundary formation and maintenance, coordinated cell movements, and the induction and maintenance of structural and functional cell and tissue polarity. Cadherins have been implicated in the formation and maintenance of diverse tissues and organs ranging from polarization of simple epithelia, to mechanically linking hair cells in the cochlea, to providing an adhesion code for neural circuit formation during wiring of the brain (Yagi and Takeichi 2000;Gumbiner 2005). Given the breadth of their functions, it is not surprising that defective cadherin expression has also been linked directly to a wide variety of diseases including the archetypal disruption of normal tissue architecture, metastatic cancer .The large size of the cadherin family and the structural diversity of its members may have evolved to enable the many types of cell interactions required for tissue morphogenesis in complex organisms. The number of cadherins as well as distinct features of their gene structure permit precise temporal and spatial transcriptional regulation of cadherin subtypes, and variations in protein structure, particularly the cytopl...

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“…2B). It is important to note that the electron-dense material found between the oocyte and the follicle cells does not correspond to yolk protein prior to its uptake by the oocyte but rather to vitelline bodies (v), which remain in the perivitelline space and will coalesce at the end of stage 10 to form the vitelline membrane around the oocyte (D'Alterio et al, 2005;Schlichting et al, 2006).…”

Section: Rab5 Is Required For Endocytosis In the Oocytementioning

confidence: 99%

Interplay between Rab5 and PtdIns(4,5)P2 controls early endocytosis in theDrosophilagermline

Compagnon

Gervais

Roman

et al. 2009

Journal of Cell Science

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Phosphoinositides have emerged as key regulators of membrane traffic through their control of the localization and activity of several effector proteins. Both Rab5 and phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] are involved in the early steps of the clathrin-dependent endocytic pathway, but little is known about how their functions are coordinated. We have studied the role of PtdIns(4,5)P2 and Rab5 in the Drosophila germline during oogenesis. We found that Rab5 is required for the maturation of early endocytic vesicles. We show that PtdIns(4,5)P2 is required for endocytic-vesicle formation, for Rab5 recruitment to endosomes and, consistently, for endocytosis. Furthermore, we reveal a previously undescribed role of Rab5 in releasing PtdIns(4,5)P2, PtdIns(4,5)P2-binding budding factors and F-actin from early endocytic vesicles. Finally, we show that overexpressing the PtdIns(4,5)P2-synthesizing enzyme Skittles leads to an endocytic defect that is similar to that seen in rab5 loss-of-function mutants. Hence, our results argue strongly in favor of the hypothesis that the Rab5-dependant release of PtdIns(4,5)P2 from endosomes that we discovered in this study is crucial for endocytosis to proceed.

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

Cited by 76 publications

References 59 publications

Hyaluronan Synthesis Induces Microvillus-like Cell Surface Protrusions

Hyaluronan Synthesis Induces Microvillus-like Cell Surface Protrusions

Cadherins in development: cell adhesion, sorting, and tissue morphogenesis

Interplay between Rab5 and PtdIns(4,5)P2 controls early endocytosis in theDrosophilagermline

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