C-terminal phosphorylation modulates ERM-1 localization and dynamics to control cortical actin organization and support lumen formation during Caenorhabditis elegans development

• Published in: Development (Cambridge) Vol. 147; no. 14
• Main Authors: Ramalho, João J, Sepers, Jorian J, Nicolle, Ophélie, Schmidt, Ruben, Cravo, Janine, Michaux, Grégoire, Boxem, Mike
• Format: Journal Article
• Language: English
• Published: England 22-07-2020
• Subjects: Actin Cytoskeleton; Actins - metabolism; Amino Acid Sequence; Animals; Binding Sites; Caenorhabditis elegans - growth & development; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - chemistry; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cytoskeletal Proteins - chemistry; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Humans; Intestinal Mucosa - metabolism; Larva - growth & development; Larva - metabolism; Mutagenesis, Site-Directed; Phosphorylation; Protein Binding; Protein Domains; Sequence Alignment; Caenorhabditis elegans; Phosphorylation; Moesin; ERM-1; Radixin; Ezrin
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.188011

ERM proteins are conserved regulators of cortical membrane specialization that function as membrane-actin linkers and molecular hubs. The 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 PIP
binding and phosphorylation of a conserved C-terminal threonine residue. Here, we use the single
ERM ortholog, ERM-1, to study the contribution of these regulatory events to ERM activity and tissue formation
Using CRISPR/Cas9-generated
mutant alleles, we demonstrate that a PIP
-binding site is crucially required for ERM-1 function. By 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.