The Sharpin interactome reveals a role for Sharpin in lamellipodium formation via the Arp2/3 complex.

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)

Interna författare/redaktörer

Publikationens författare: Khan, Salomaa, Jacquemet, Butt, Miihkinen, Deguchi, Kremneva, Lappalainen, Humphries, Pouwels
Publiceringsår: 2017
Tidskrift: Journal of Cell Science
Tidskriftsakronym: J Cell Sci
Volym: 130
Nummer: 18
Artikelns första sida, sidnummer: 3094
Artikelns sista sida, sidnummer: 3107
ISSN: 1477-9137


Sharpin, a multifunctional adaptor protein, regulates several signalling pathways. For example, Sharpin enhances signal-induced NF-κB signalling as part of the linear ubiquitin assembly complex (LUBAC) and inhibits integrins, the T cell receptor, caspase 1 and PTEN. However, despite recent insights into Sharpin and LUBAC function, a systematic approach to identify the signalling pathways regulated by Sharpin has not been reported. Here, we present the first 'Sharpin interactome', which identifies a large number of novel potential Sharpin interactors in addition to several known ones. These data suggest that Sharpin and LUBAC might regulate a larger number of biological processes than previously identified, such as endosomal trafficking, RNA processing, metabolism and cytoskeleton regulation. Importantly, using the Sharpin interactome, we have identified a novel role for Sharpin in lamellipodium formation. We demonstrate that Sharpin interacts with Arp2/3, a protein complex that catalyses actin filament branching. We have identified the Arp2/3-binding site in Sharpin and demonstrate using a specific Arp2/3-binding deficient mutant that the Sharpin-Arp2/3 interaction promotes lamellipodium formation in a LUBAC-independent fashion.This article has an associated First Person interview with the first author of the paper.

Senast uppdaterad 2019-13-11 vid 04:52