TY - JOUR
T1 - Ca2+-dependent protein acyltransferase DHHC21 controls activation of CD4+ T cells
AU - Bieerkehazhi, Shayahati
AU - Fan, Ying
AU - West, Savannah J.
AU - Tewari, Ritika
AU - Ko, Junsuk
AU - Mills, Tingting
AU - Boehning, Darren
AU - Akimzhanov, Askar M.
N1 - Publisher Copyright:
© 2021. Published by The Company of Biologists Ltd
PY - 2021/3
Y1 - 2021/3
N2 - Despite the recognized significance of reversible protein lipidation (S-acylation) for T cell receptor signal transduction, the enzymatic control of this post-translational modification in T cells remains poorly understood. Here, we demonstrate that DHHC21 (also known as ZDHHC21), a member of the DHHC family of mammalian protein acyltransferases, mediates T cell receptor-induced S-acylation of proximal T cell signaling proteins. Using Zdhhc21dep mice, which express a functionally deficient version of DHHC21, we show that DHHC21 is a Ca2+/calmodulin-dependent enzyme critical for activation of naïve CD4+ T cells in response to T cell receptor stimulation. We find that disruption of the Ca2+/calmodulin-binding domain of DHHC21 does not affect thymic T cell development but prevents differentiation of peripheral CD4+ T cells into Th1, Th2 and Th17 effector T helper lineages. Our findings identify DHHC21 as an essential component of the T cell receptor signaling machinery and define a new role for protein acyltransferases in regulation of T cell-mediated immunity.
AB - Despite the recognized significance of reversible protein lipidation (S-acylation) for T cell receptor signal transduction, the enzymatic control of this post-translational modification in T cells remains poorly understood. Here, we demonstrate that DHHC21 (also known as ZDHHC21), a member of the DHHC family of mammalian protein acyltransferases, mediates T cell receptor-induced S-acylation of proximal T cell signaling proteins. Using Zdhhc21dep mice, which express a functionally deficient version of DHHC21, we show that DHHC21 is a Ca2+/calmodulin-dependent enzyme critical for activation of naïve CD4+ T cells in response to T cell receptor stimulation. We find that disruption of the Ca2+/calmodulin-binding domain of DHHC21 does not affect thymic T cell development but prevents differentiation of peripheral CD4+ T cells into Th1, Th2 and Th17 effector T helper lineages. Our findings identify DHHC21 as an essential component of the T cell receptor signaling machinery and define a new role for protein acyltransferases in regulation of T cell-mediated immunity.
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U2 - 10.1242/jcs.258186
DO - 10.1242/jcs.258186
M3 - Article
C2 - 34080635
AN - SCOPUS:85108323479
SN - 0021-9533
VL - 135
JO - Journal of cell science
JF - Journal of cell science
IS - 5
M1 - jcs258186
ER -