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  • The Bardet-Biedl syndrome complex component BBS1 controls T cell polarity during immune synapse assembly.

The Bardet-Biedl syndrome complex component BBS1 controls T cell polarity during immune synapse assembly.

Journal of cell science (2021-08-24)
Chiara Cassioli, Anna Onnis, Francesca Finetti, Nagaja Capitani, Jlenia Brunetti, Ewoud B Compeer, Veronika Niederlova, Ondrej Stepanek, Michael L Dustin, Cosima T Baldari
ABSTRACT

Components of the intraflagellar transport (IFT) system that regulates the assembly of the primary cilium are co-opted by the non-ciliated T cell to orchestrate polarized endosome recycling and to sustain signaling during immune synapse formation. Here, we investigated the potential role of Bardet-Biedl syndrome 1 protein (BBS1), an essential core component of the BBS complex that cooperates with the IFT system in ciliary protein trafficking, in the assembly of the T cell synapse. We demonstrated that BBS1 allows for centrosome polarization towards the immune synapse. This function is achieved through the clearance of centrosomal F-actin and its positive regulator WASH1 (also known as WASHC1), a process that we demonstrated to be dependent on the proteasome. We show that BBS1 regulates this process by coupling the 19S proteasome regulatory subunit to the microtubule motor dynein for its transport to the centrosome. Our data identify the ciliopathy-related protein BBS1 as a new player in T cell synapse assembly that functions upstream of the IFT system to set the stage for polarized vesicular trafficking and sustained signaling. This article has an associated First Person interview with the first author of the paper.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MG-132, Ready Made Solution, ≥90% (HPLC)
Sigma-Aldrich
Cytoplasmic Dynein Inhibitor, Ciliobrevin D, Ciliobrevin D is a cell-permeable, reversible, and specific blocker of AAA+ ATPase motor cytoplasmic dynein. Disrupts spindle pole focusing and kinetochore-microtubule attachment (~10 to 40 µM).
Sigma-Aldrich
Puromycin dihydrochloride from Streptomyces alboniger, powder, BioReagent, suitable for cell culture