Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration
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Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration. / Law, Ah-Lai; Jalal, 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.
In: NAT COMMUN, Vol. 12, No. 1, 28.09.2021, p. 5687.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration
AU - Law, Ah-Lai
AU - Jalal, Shamsinar
AU - Pallett, Tommy
AU - Mosis, Fuad
AU - Guni, Ahmad
AU - Brayford, Simon
AU - Yolland, Lawrence
AU - Marcotti, Stefania
AU - Levitt, James A
AU - Poland, Simon P
AU - Rowe-Sampson, Maia
AU - Jandke, Anett
AU - Köchl, Robert
AU - Pula, Giordano
AU - Ameer-Beg, Simon M
AU - Stramer, Brian Marc
AU - Krause, Matthias
N1 - © 2021. The Author(s).
PY - 2021/9/28
Y1 - 2021/9/28
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-021-25916-6
DO - 10.1038/s41467-021-25916-6
M3 - SCORING: Journal article
C2 - 34584076
VL - 12
SP - 5687
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -