Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration
Authors
Law, Ah-LaiJalal, Shamsinar
Pallett, Tommy
Mosis, Fuad
Guni, Ahmad
Brayford, Simon
Yolland, Lawrence
Marcotti, Stefania
Levitt, James A.
Poland, Simon P.
Rowe-Sampson, Maia
Jandke, Anett
Köchl, Robert
Pula, Giordano
Ameer-Beg, Simon M.
Stramer, Brian Marc
Krause, Matthias
Affiliation
King’s College LondonUniversity of Bedfordshire
Francis Crick Institute
University Medical Center Hamburg
Issue Date
2021-09-28
Metadata
Show full item recordAbstract
Cell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate it. However, so far, no direct negative regulators are known. Here we identify Nance-Horan Syndrome-like 1 protein (NHSL1) as a direct binding partner of the Scar/WAVE complex, which co-localise at protruding lamellipodia. This interaction is mediated by the Abi SH3 domain and two binding sites in NHSL1. Furthermore, active Rac binds to NHSL1 at two regions that mediate leading edge targeting of NHSL1. Surprisingly, NHSL1 inhibits cell migration through its interaction with the Scar/WAVE complex. Mechanistically, NHSL1 may reduce cell migration efficiency by impeding Arp2/3 activity, as measured in cells using a Arp2/3 FRET-FLIM biosensor, resulting in reduced F-actin density of lamellipodia, and consequently impairing the stability of lamellipodia protrusions.Citation
Law AL, Jalal S, Pallett T, Mosis F, Guni A, Brayford S, Yolland L, Marcotti S, Levitt JA, Poland SP, Rowe-Sampson M, Jandke A, Köchl R, Pula G, Ameer-Beg SM, Stramer BM, Krause M (2021) 'Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration', Nature Communications, 12 (1), .5687.Publisher
Nature ResearchJournal
Nature CommunicationsPubMed ID
34584076PubMed Central ID
PMC8478917Additional Links
https://www.nature.com/articles/s41467-021-25916-6Type
ArticleLanguage
enEISSN
2041-1723ae974a485f413a2113503eed53cd6c53
10.1038/s41467-021-25916-6
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