A role for SHARPIN in platelet linear protein ubiquitination and function – By Moore et al. (2021).

Background

Src homology 3 and multiple ankyrin repeat domains protein (SHANK)-associated RH domain-interacting protein (SHARPIN). SHARPIN modulates immune and inflammatory responses. A spontaneous null mutation in the SHARPIN gene in mice results in chronic proliferative dermatitis, multi-organ inflammation, and increased expression of inflammatory cytokines.

The molecular mechanism behind these events could be SHARPIN’s role in regulating the activation of NfkB as part of the linear ubiquitin chain assembly complex (LUBAC), responsible for regulating many cell signaling pathways.

Ubiquitination and NfKB play a role in platelet function. Additionally, SHARPIN negatively regulates integrin and can also regulate platelet function by activating the NfkB pathway.

Until now, there’s little information about linear ubiquitination or SHARPIN in mouse platelets. So, researchers at the University of Bristol (UK), evaluated platelet function in mice with impaired SHARPIN expression.

Methods

To assess the role of SHARPIN in regulating platelet function, the researchers used C57BL/KaLawRij-SHARPINcpdm/RijSunJ (cpdm) mouse line. The cpdm mutation results in the loss of SHARPIN protein expression. The group evaluated if these mice had altered thrombus formation. For that, they tested the ability of cpdm/cpdm platelet to