T Cell Receptor (TCR)-Induced PLC-γ1 Sumoylation Via PIASxβ and PIAS3 SUMO E3 Ligases Regulates the Microcluster Assembly and Physiological Function of PLC-γ1

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2019 Mar 16

PMID 30873169

Citations 9

Authors

Qi-Long Wang

Jia-Qi Liang

Bei-Ni Gong

Ji-Ji Xie

Yu-Ting Yi

Xin Lan

Yingqiu Li

Affiliations

Soon will be listed here.

Abstract

The SUMO modification system plays an important role in T cell activation, yet how sumoylation regulates TCR-proximal signaling remains largely unknown. We show here that Phospholipase C-γ1 (PLC-γ1) is conjugated by SUMO1 at K54 and K987 upon TCR stimulation and that K54 sumoylation is pivotal for PLC-γ1-mediated T cell activation. We further demonstrate that TCR-induced K54 sumoylation of PLC-γ1 significantly promotes the formation of PLC-γ1 microclusters and the association of PLC-γ1 with the adaptor proteins SLP76 and Gads, but only slightly affects the phosphorylation of PLC-γ1 on Y783, which determines the enzyme catalytic activity. Moreover, upon TCR stimulation, the SUMO E3 ligases PIASxβ and PIAS3 both interact with PLC-γ1 and cooperate to sumoylate PLC-γ1, facilitating the assembly of PLC-γ1 microclusters. Together, our findings reveal a critical role of PLC-γ1 K54 sumoylation in PLC-γ1 microcluster assembly that controls PLC-γ1-mediated T cell activation, suggesting that sumoylation may have an important role in the microcluster assembly of TCR-proximal signaling proteins.

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