{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:33:56Z","timestamp":1792024436416,"version":"4.4.0"},"reference-count":39,"publisher":"The Company of Biologists","issue":"23","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008967","name":"Philipps-Universit\u00e4t Marburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008967","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The WAVE regulatory complex (WRC) is the main activator of the Arp2\/3 complex, promoting lamellipodial protrusions in migrating cells. The WRC is basally inactive but can be activated by Rac1 and phospholipids, and through phosphorylation. However, the in vivo relevance of the phosphorylation of WAVE proteins remains largely unknown. Here, we identified casein kinase I alpha (CK1\u03b1) as a regulator of WAVE, thereby controlling cell shape and cell motility in Drosophila macrophages. CK1\u03b1 binds and phosphorylates WAVE in vitro. Phosphorylation of WAVE by CK1\u03b1 appears not to be required for activation but, rather, regulates its stability. Pharmacologic inhibition of CK1\u03b1 promotes ubiquitin-dependent degradation of WAVE. Consistently, loss of Ck1\u03b1 but not ck2 function phenocopies the depletion of WAVE. Phosphorylation-deficient mutations in the CK1\u03b1 consensus sequences within the VCA domain of WAVE can neither rescue mutant lethality nor lamellipodium 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 CK1\u03b1-depleted macrophages. Therefore, we conclude that basal phosphorylation of WAVE by CK1\u03b1 protects it from premature ubiquitin-dependent degradation, thus promoting WAVE function in vivo.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/jcs.258891","type":"journal-article","created":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T11:20:33Z","timestamp":1635938433000},"source":"Crossref","is-referenced-by-count":11,"title":["CK1\u03b1 protects WAVE from degradation to regulate cell shape and motility in the immune response"],"prefix":"10.1242","volume":"134","author":[{"given":"Alexander","family":"Hirschh\u00e4user","sequence":"first","affiliation":[{"name":"Institute of Physiology and Pathophysiology 1 , Dept. of Molecular Cell Physiology , , 35037 Marburg ,","place":["Germany"]},{"name":"Philipps-University Marburg 1 , Dept. of Molecular Cell Physiology , , 35037 Marburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6388-4937","authenticated-orcid":false,"given":"Marianne","family":"van Cann","sequence":"additional","affiliation":[{"name":"Institute for Neurobiology, University of M\u00fcnster 2 , 48149 M\u00fcnster ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8753-9855","authenticated-orcid":false,"given":"Sven","family":"Bogdan","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Pathophysiology 1 , Dept. of Molecular Cell Physiology , , 35037 Marburg ,","place":["Germany"]},{"name":"Philipps-University Marburg 1 , Dept. of Molecular Cell Physiology , , 35037 Marburg ,","place":["Germany"]},{"name":"Institute for Neurobiology, University of M\u00fcnster 2 , 48149 M\u00fcnster ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"2024111909115658500_JCS258891C1","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/nmeth1048","article-title":"A semisynthetic epitope for kinase substrates","volume":"4","author":"Allen","year":"2007","journal-title":"Nat. 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