Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration

Ah-Lai Law, Shamsinar Jalal, Tommy Pallett, Fuad Mosis, Ahmad Guni, Simon Brayford, Lawrence Yolland, Stefania Marcotti, James A. Levitt, Simon P. Poland, Maia Rowe-Sampson, Anett Jandke, Robert Köchl, Giordano Pula, Simon M. Ameer-Beg, Brian Marc Stramer and Matthias Krause ()
Additional contact information
Ah-Lai Law: King’s College London
Shamsinar Jalal: King’s College London
Tommy Pallett: King’s College London
Fuad Mosis: King’s College London
Ahmad Guni: King’s College London
Simon Brayford: King’s College London
Lawrence Yolland: King’s College London
Stefania Marcotti: King’s College London
James A. Levitt: King’s College London
Simon P. Poland: King’s College London
Maia Rowe-Sampson: King’s College London
Anett Jandke: King’s College London
Robert Köchl: King’s College London
Giordano Pula: King’s College London
Simon M. Ameer-Beg: King’s College London
Brian Marc Stramer: King’s College London
Matthias Krause: King’s College London

Nature Communications, 2021, vol. 12, issue 1, 1-20

Abstract: Abstract 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25916-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25916-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25916-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().