Open AccessC-terminal phosphorylation modulates ERM-1 localization and dynamics to control cortical actin organization and support lumen formation during C. elegans development
Author(s) -
João J. Ramalho,
Jorian J. Sepers,
Ophélie Nicolle,
Ruben Schmidt,
Janine Cravo,
Grégoire Michaux,
Mike Boxem
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.188011
Subject(s) - biology , microbiology and biotechnology , phosphorylation , actin , moesin , actin binding protein , subcellular localization , ezrin , cytoplasm , biochemistry , actin cytoskeleton , cytoskeleton , cell
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 actin-bound 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 a PIP2-binding site is critically required for ERM-1 function. In contrast, dynamic regulation of C-terminal T544 phosphorylation is not essential but modulates ERM-1 apical localization and dynamics in a tissue-specific manner, to control cortical actin organization and support 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.