RRC ID 68673
著者 Hirschhäuser A, van Cann M, Bogdan S.
タイトル CK1α protects WAVE from degradation to regulate cell shape and motility in the immune response.
ジャーナル J Cell Sci
Abstract The WAVE regulatory complex (WRC) is the major Arp2/3 activator, promoting lamellipodial protrusions in migrating cells. The WRC is basally inactive but can be activated by Rac1 and phospholipids, and phosphorylation. However, the in vivo relevance of phosphorylation of WAVE remains largely unknown. Here, we identified the kinase CK1α as a novel regulator of WAVE controlling cell shape and cell motility in Drosophila macrophages. CK1α binds and phosphorylates WAVE in vitro. Phosphorylation of WAVE by CK1α appears not to be required for activation but rather regulates its stability. Pharmacologic inhibition of CK1α promotes ubiquitin-dependent degradation of WAVE. Consistently, loss of ck1α but not ck2 function phenocopies WAVE depletion. Phosphorylation-deficient mutations in the CK1α consensus sequences within the VCA domain of WAVE can neither rescue mutant lethality nor lamellipodia defects. By contrast, phosphomimetic mutations rescue all cellular and developmental defects. Finally, RNAi-mediated suppression of 26S proteasome or E3 ligase complexes substantially rescues lamellipodia defects in CK1α depleted macrophages. Thus, we conclude that the basal phosphorylation of WAVE by CK1α protects it from premature ubiquitin-dependent degradation, thus promoting WAVE function in vivo.
巻・号 134(23)
公開日 2021-12-1
DOI 10.1242/jcs.258891
PII 272700
PMID 34730182
PMC PMC8714073
MeSH Casein Kinase Ialpha* / genetics Casein Kinase Ialpha* / metabolism Cell Shape Humans Immunity Phosphorylation Wiskott-Aldrich Syndrome Protein Family / metabolism
IF 4.573
リソース情報
ショウジョウバエ 10260Rb-1 10260Rb-2 14030R-1 14030R-2 2055R-1 9774R-2 9774R-3