In vivocontrol of the ezrin/radixin/moesin protein ERM-1 inC. elegans

Abstract

ERM proteins are conserved regulators of cortical membrane specialization, that function as membrane-actin linkers and molecular hubs. Activity of ERM proteins requires a conformational switch from an inactive cytoplasmic form into an active membrane-and actinbound form, which is thought to be mediated by sequential PIP2-binding and phosphorylation of a conserved C-terminal threonine residue. Here, we use the single C. elegans ERM ortholog, ERM-1, to study the contribution of these regulatory events to ERM activity and tissue formation in vivo. Using CRISPR/Cas9-generated erm-1 mutant alleles we demonstrate that PIP2-binding is critically required for ERM-1 function. In contrast, dynamic regulation of Cterminal T544 phosphorylation is not essential but modulates ERM-1 apical localization and dynamics in a tissue-specific manner, to control cortical actin organization and drive lumen formation in epithelial tubes. Our work highlights the dynamic nature of ERM protein regulation during tissue morphogenesis and the importance of C-terminal phosphorylation in fine-tuning ERM activity in a tissue-specific context.