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Fabio Demontis

Publications and source records attributed to Fabio Demontis.

5 recordsLinked to original sources
PubMed2006

PDZ-domain-binding sites are common among cadherins.

Cadherins are Ca(2+)-dependent cell adhesion molecules that play fundamental roles in animal development and homeostasis. A number of cadherins contain conserved binding sites for catenins in their cytoplasmic region that are important for the adhesive function of these cadherins by mediating their interaction to the cytoskeleton. However, most cadherins lack apparent binding sites for catenins and their cytoplasmic interacting partners are mostly unknown. In this paper, we show, using bioinformatics, that a number of insect and vertebrate cadherins lacking catenin-binding sites contain conserved consensus sequences for C-terminal PSD-95/Discs-large/ZO-1 (PDZ)-domain-binding sites. This suggests that PDZ-domain-containing proteins are common cytoplasmic interacting partners for cadherins lacking catenin-binding sites.

Amino Acid Sequence↗
PubMed2006

Cadherin Cad99C is required for normal microvilli morphology in Drosophila follicle cells.

Microvilli are actin-filled membranous extensions common to epithelial cells. Several proteins have been identified that localize to microvilli. However, most of these proteins are dispensable for the normal morphogenesis of microvilli. Here, we show by immunoelectron microscopy that the non-classical cadherin Cad99C localizes to microvilli of Drosophila ovarian follicle cells. Loss of Cad99C function leads to disorganized and abnormal follicle cell microvilli. Conversely, overexpression of Cad99C in follicle cells results in large bundles of microvilli. Furthermore, altered microvilli morphology correlates with defects in the assembly of the vitelline membrane, an extracellular layer secreted by follicle cells that is part of the eggshell. Finally, we provide evidence that Cad99C is the homolog of vertebrate protocadherin 15. Mutations in the gene encoding protocadherin 15 lead to the disorganization of stereocilia, which are microvilli-derived extensions of cochlear hair cells, and deafness (Usher syndrome type 1F). Our data suggest an essential role for Cad99C in microvilli morphogenesis that is important for follicle cell function. Furthermore, these results indicate that insects and vertebrates use related cadherins to organize microvilli-like cellular extensions.

Animals↗
PubMed2005

Cadherin Cad99C is regulated by Hedgehog signaling in Drosophila.

The subdivision of the Drosophila wing imaginal disc into anterior and posterior compartments requires a transcriptional response to Hedgehog signaling. However, the genes regulated by Hedgehog signal transduction that mediate the segregation of anterior and posterior cells have not been identified. Here, we molecularly characterize the previously predicted gene cad99C and show that it is regulated by Hedgehog signaling. Cad99C encodes a transmembrane protein with a molecular weight of approximately 184 kDa that contains 11 cadherin repeats in its extracellular domain and a conserved type I PDZ-binding site at its C-terminus. The levels of cad99C RNA and protein are low throughout the wing imaginal disc. However, in the pouch region, these levels are elevated in a strip of anterior cells along the A/P boundary where the Hedgehog signal is transduced. Ectopic expression of Hedgehog, or the Hedgehog-regulated transcription factor Cubitus interruptus, induces high-level expression of Cad99C. Conversely, blocking Hedgehog signal transduction by either inactivating Smoothened or Cubitus interruptus reduces high-level Cad99C expression. Finally, by analyzing mutant clones of cells, we show that Cad99C is not essential for cell segregation at the A/P boundary. We conclude that cad99C is a novel Hedgehog-regulated gene encoding a member of the cadherin superfamily in Drosophila.

Amino Acid Sequence↗
PubMed2004

VE-cadherin expression and clustering maintain low levels of survivin in endothelial cells.

Survivin is strongly expressed in embryonic organs and in tumor cells but is low or absent in differentiated normal tissues. Resting endothelium expresses low levels of survivin but can up-regulate its synthesis on activation to proliferate. The mechanisms responsible for survivin down-regulation in resting conditions are still unknown. We report here that confluence and vascular endothelial-cadherin (VE-cadherin) expression induce contact inhibition of cell growth and survivin down-regulation in the endothelium. Using beta-catenin null and positive isogenic endothelial cell lines we found that the effect requires beta-catenin expression and its association to VE-cadherin cytoplasmic tail. Furthermore, in allantois organ cultures, survivin expression is up-regulated in areas of growing vessels where VE-cadherin is partially dismantled from junctions or in VE-cadherin -/- specimens. Overall, these data indicate that VE-cadherin and beta-catenin may negatively regulate survivin synthesis in endothelial cells. Consistently, in epidermal and pancreatic cell lines or ovarian tumors, epithelial-cadherin (E-cadherin) and survivin expression is inversely related, suggesting a non-cell-specific role of cadherins in reducing survivin synthesis.

Allantois↗