The Sharpin interactome reveals a role for Sharpin in lamellipodium formation via the Arp2/3 complex
: Meraj H. Khan, Siiri I. Salomaa, Guillaume Jacquemet, Umar Butt, Mitro Miihkinen, Takahiro Deguchi, Elena Kremneva, Pekka Lappalainen, Martin J. Humphries, Jeroen Pouwels
Publisher: The Company of Biologists Ltd
: 2017
: Journal of Cell Science
: 130
: 18
: 3094
: 3107
: 14
: 0021-9533
: 1477-9137
DOI: https://doi.org/10.1242/jcs.200329
: https://research.utu.fi/converis/portal/detail/Publication/24938313
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, caspase1 and PTEN. However, despite
recent insights into Sharpin and LUBAC function, a systematic approach
to identify signalling pathways regulated by Sharpin has not been
reported. Here, we present the first ‘Sharpin interactome’, which
identifies a large amount 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 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.
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