RRC ID 51530
Author Sasidharan S, Borinskaya S, Patel F, Bernadskaya Y, Mandalapu S, Agapito M, Soto MC.
Title WAVE regulates Cadherin junction assembly and turnover during epithelial polarization.
Journal Dev Biol
Abstract Actin is an integral component of epithelial apical junctions, yet the interactions of branched actin regulators with apical junction components are still not clear. Biochemical data have shown that α-catenin inhibits Arp2/3-dependent branched actin. These results suggested that branched actin is only needed at earliest stages of apical junction development. We use live imaging in developing C. elegans embryos to test models for how WAVE-induced branched actin collaborates with other apical junction proteins during the essential process of junction formation and maturation. We uncover both early and late essential roles for WAVE in apical junction formation. Early, as the C. elegans intestinal epithelium becomes polarized, we find that WAVE components become enriched concurrently with the Cadherin components and before the DLG-1 apical accumulation. Live imaging of F-actin accumulation in polarizing intestine supports that the Cadherin complex components and branched actin regulators work together for apical actin enrichment. Later in junction development, the apical accumulation of WAVE and Cadherin components is shown to be interdependent: Cadherin complex loss alters WAVE accumulation, and WAVE complex loss increases Cadherin accumulation. To determine why Cadherin levels rise when WVE-1 is depleted, we use FRAP to analyze Cadherin dynamics and find that loss of WAVE as well as of the trafficking protein EHD-1/RME-1 increases Cadherin dynamics. EM studies in adults depleted of branched actin regulators support that WVE-1 maintains established junctions, presumably through its trafficking effect on Cadherin. Thus we propose a developmental model for junction formation where branched actin regulators are tightly interconnected with Cadherin junctions through their previously unappreciated role in Cadherin transport.
Volume 434(1)
Pages 133-148
Published 2018-2-1
DOI 10.1016/j.ydbio.2017.12.002
PII S0012-1606(17)30694-2
PMID 29223862
PMC PMC5812483
MeSH Animals Cadherins / genetics Cadherins / metabolism* Caenorhabditis elegans / embryology* Caenorhabditis elegans / genetics Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Polarity / physiology* Embryo, Nonmammalian / cytology Embryo, Nonmammalian / embryology* Embryo, Nonmammalian / ultrastructure Epithelial Cells / metabolism* Epithelial Cells / ultrastructure Tight Junctions / genetics Tight Junctions / metabolism* Tight Junctions / ultrastructure
IF 2.936
Times Cited 2
C.elegans tm597