Regulation of microtubule detyrosination by Ca2+ and conventional calpains
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Regulation of microtubule detyrosination by Ca2+ and conventional calpains. / Bär, Julia; Popp, Yannes; Koudelka, Tomas; Tholey, Andreas; Mikhaylova, Marina.
in: J CELL SCI, Jahrgang 135, Nr. 9, jcs259108, 01.05.2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Regulation of microtubule detyrosination by Ca2+ and conventional calpains
AU - Bär, Julia
AU - Popp, Yannes
AU - Koudelka, Tomas
AU - Tholey, Andreas
AU - Mikhaylova, Marina
N1 - © 2022. Published by The Company of Biologists Ltd.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Detyrosination is a major post-translational modification of microtubules (MTs), which has significant impact on MT function in cell division, differentiation, growth, migration and intracellular trafficking. Detyrosination of α-tubulin occurs mostly via the recently identified complex of vasohibin 1 or 2 (VASH1 and VASH2, respectively) with small vasohibin binding protein (SVBP). However, there is still remaining detyrosinating activity in the absence of VASH1 and/or VASH2 and SVBP, and little is known about the regulation of detyrosination. Here, we found that intracellular Ca2+ is required for efficient MT detyrosination. Furthermore, we show that the Ca2+-dependent proteases calpains 1 and 2 (CAPN1 and CAPN2, respectively) regulate MT detyrosination in VASH1- and SVBP-overexpressing human embryonic kidney (HEK293T) cells. We identified new calpain cleavage sites in the N-terminal disordered region of VASH1. However, this cleavage did not affect the enzymatic activity of vasohibins. In conclusion, we suggest that the regulation of VASH1-mediated MT detyrosination by calpains could occur independently of vasohibin catalytic activity or via another yet unknown tubulin carboxypeptidase. Importantly, the Ca2+ dependency of calpains could allow a fine regulation of MT detyrosination. Thus, identifying the calpain-regulated pathway of MT detyrosination can be of major importance for basic and clinical research.
AB - Detyrosination is a major post-translational modification of microtubules (MTs), which has significant impact on MT function in cell division, differentiation, growth, migration and intracellular trafficking. Detyrosination of α-tubulin occurs mostly via the recently identified complex of vasohibin 1 or 2 (VASH1 and VASH2, respectively) with small vasohibin binding protein (SVBP). However, there is still remaining detyrosinating activity in the absence of VASH1 and/or VASH2 and SVBP, and little is known about the regulation of detyrosination. Here, we found that intracellular Ca2+ is required for efficient MT detyrosination. Furthermore, we show that the Ca2+-dependent proteases calpains 1 and 2 (CAPN1 and CAPN2, respectively) regulate MT detyrosination in VASH1- and SVBP-overexpressing human embryonic kidney (HEK293T) cells. We identified new calpain cleavage sites in the N-terminal disordered region of VASH1. However, this cleavage did not affect the enzymatic activity of vasohibins. In conclusion, we suggest that the regulation of VASH1-mediated MT detyrosination by calpains could occur independently of vasohibin catalytic activity or via another yet unknown tubulin carboxypeptidase. Importantly, the Ca2+ dependency of calpains could allow a fine regulation of MT detyrosination. Thus, identifying the calpain-regulated pathway of MT detyrosination can be of major importance for basic and clinical research.
U2 - 10.1242/jcs.259108
DO - 10.1242/jcs.259108
M3 - SCORING: Journal article
C2 - 35373296
VL - 135
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - 9
M1 - jcs259108
ER -