The transmembrane protein Crumbs displays complex dynamics during follicular morphogenesis and is regulated competitively by Moesin and aPKC

Abstract

There was an error published in Development 142, 1869-1878.On p. 1869, the sentence 'Recently, the JM domain was implicated in specifying the position of a supercellular actomyosin cable, by concentrating atypical protein kinase C (aPKC) away from the site of the cable, thereby allowing an increase in localized Rhomboid (Rho) activity (Roper, 2012).' should instead have read:'Recently, the JM domain was implicated in specifying the position of a supercellular actomyosin cable, by concentrating atypical protein kinase C (aPKC) away from the site of the cable, thereby allowing an increase in localized Rho-kinase (Rok) activity (Roper, 2012).'The publishers and authors apologise to readers for this mistake. 2226 ABSTRACTThe transmembrane protein Crumbs (Crb) functions in apical polarity and epithelial integrity. To better understand its role in epithelial morphogenesis, we examined Crb localization and dynamics in the late follicular epithelium of Drosophila. Crb was unexpectedly dynamic during middle-to-late stages of egg chamber development, being lost from the marginal zone (MZ) in stage 9 before abruptly returning at the end of stage 10b, then undergoing a pulse of endocytosis in stage 12. The reappearance of MZ Crb is necessary to maintain an intact adherens junction and MZ. Although Crb has been proposed to interact through its juxtamembrane domain with Moesin (Moe), a FERM domain protein that regulates the cortical actin cytoskeleton, the functional significance of this interaction is poorly understood. We found that whereas the Crb juxtamembrane domain was not required for adherens junction integrity, it was necessary for MZ localization of Moe, aPKC and F-actin. Furthermore, Moe and aPKC functioned antagonistically, suggesting that Moe limits Crb levels by reducing its interactions with the apical Par network. Additionally, Moe mutant cells lost Crb from the apical membrane and accumulated excess Crb at the MZ, suggesting that Moe regulates Crb distribution at the membrane. Together, these studies reveal reciprocal interactions between Crb, Moe and aPKC during cellular morphogenesis.

The transmembrane protein Crb2a regulates cardiomyocyte apicobasal polarity and adhesion in zebrafish

“…Accordingly, CMs have been reported to exhibit substantial cellular plasticity during trabeculation, losing their cobblestone-like shape once they start delaminating (Liu et al, 2010;Staudt et al, 2014). Our observations are consistent with previous reports in Drosophila where during follicular morphogenesis as cells change shape, Crb is lost from the marginal zone (the most apical surface), relocalizes to the AJ and subsequently reappears at the marginal zone (Sherrard and Fehon, 2015;Wu et al, 2016). We found that blocking Nrg/ErbB2 signaling leads to relocalization of Crb2a from the junctions to the apical surface of CMs.…”

“…We found that blocking Nrg/ErbB2 signaling leads to relocalization of Crb2a from the junctions to the apical surface of CMs. Interestingly, in Drosophila, depletion of cytoskeletal proteins required for Crb localization leads to relocalization of apical Crb to the junctions (Sherrard and Fehon, 2015). These data indicate that Crb2a localization is very dynamic and that Nrg/ErbB2 signaling, which is essential for cardiac trabeculation, is required for its junctional to apical shift.…”

Crumbs is an essential regulator of cytoskeletal dynamics and cell-cell adhesion during dorsal closure in Drosophila

“…Similarly, mutating Tyr10 in the FBM of the intercellular adhesion molecule (ICAM)-2 or the equivalent Tyr residue in the FBM of the neural cell adhesion molecule L1 impairs interaction with the FERM proteins radixin and ezrin, respectively ( Hamada et al, 2003 ; Cheng et al, 2005 ). Moreover, it has been shown recently that the FBM of Crb is necessary for organising D Moe, aPKC and the actin cytoskeleton at the marginal zone in the developing follicular epithelium ( Sherrard and Fehon, 2015 ). And in cervical carcinoma cells, over-expression of the mammalian CRB3 protein restores an epithelial-like morphology by organising a cortical actomyosin network through the regulation of the p114RhoGEF-RhoA-ROCK1/2 pathway via the FERM protein Ehm2 ( Loie et al, 2015 ).…”

Neuralized regulates Crumbs endocytosis and epithelium morphogenesis via specific Stardust isoforms

“…Crb and Sdt are required to stabilize epithelia (Grawe et al, 1996;Tepass, 1996;Bachmann et al, 2001;Hong et al, 2001;Campbell et al, 2009) and to negatively regulate actomyosin during tissue remodeling (Röper, 2012;Flores-Benitez and Knust, 2015). Consistent with this, changes in Crb protein levels, subcellular localization, and/or gene expression correlated with various epithelial remodeling events (Campbell et al, 2011;Röper, 2012;Sherrard and Fehon, 2015). Additionally, the crb and sdt genes encode multiple isoforms in Drosophila melanogaster.…”