title: Non-junctional E-Cadherin Clusters Regulate the Actomyosin Cortex in the C. elegans Zygote.
abstract: Classical cadherins are well known for their essential function in mediating cell-cell adhesion via their extra-cellular cadherin domains and intra-cellular connections to the actin cytoskeleton [1-3]. There is evidence, however, of adhesion-independent cadherin clusters existing outside of cell-cell junctions [4-6]. What function, if any, these clusters have is not known. HMR-1, the sole classical cadherin in Caenorhabditis elegans, plays essential roles during gastrulation, blastomere polarity establishment, and epidermal morphogenesis [7-11]. To elucidate the physiological roles of non-junctional cadherin, we analyzed HMR-1 in the C. elegans zygote, which is devoid of neighbors. We show that non-junctional clusters of HMR-1 form during the one-cell polarization stage and associate with F-actin at the cortex during episodes of cortical flow. Non-junctional HMR-1 clusters downregulate RHO-1 activity and inhibit accumulation of non-muscle myosin II (NMY-2) at the anterior cortex. We found that HMR-1 clusters impede cortical flows and play a role in preserving the integrity of the actomyosin cortex, preventing it from splitting in two. Importantly, we uncovered an inverse relationship between the amount of HMR-1 at the cell surface and the rate of cytokinesis. The effect of HMR-1 clusters on cytokinesis is independent of their effect on NMY-2 levels, and is also independent of their extra-cellular domains. Thus, in addition to their canonical role in inter-cellular adhesion, HMR-1 clusters regulate RHO-1 activity and NMY-2 level at the cell surface, reinforce the stability of the actomyosin cortex, and resist its movement to influence cell-shape dynamics.
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore.
authors.forename: Anup
authors.initials: A
authors.lastname: Padmanabhan
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore.
authors.forename: Hui Ting
authors.initials: HT
authors.lastname: Ong
authors.affiliation: Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore; Department of Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3, Singapore 117583, Singapore. Electronic address: biezbr@nus.edu.sg.
authors.forename: Ronen
authors.initials: R
authors.lastname: Zaidel-Bar
mesh_terms: D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D048749:Cytokinesis; D005786:Gene Expression Regulation; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D015053:Zygote / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; C480837:NMY-2 protein, C elegans; D000205:Actomyosin; D018995:Myosin Heavy Chains; C560609:RHO-1 protein, C elegans; D020741:rho GTP-Binding Proteins
keywords: C. elegans; HMR-1; NMY-2; RHO; actin cortex; cadherin; cluster; cytokinesis; myosin II; non-junctional