Article ; Online: Regulation of microtubule detyrosination by Ca2+ and conventional calpains.
2022 Volume 135, Issue 9
Abstract: 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 ...
Abstract | 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. |
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MeSH term(s) | Angiogenic Proteins/metabolism ; Calcium/metabolism ; Calpain/metabolism ; Carrier Proteins/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; HEK293 Cells ; Humans ; Microtubules/metabolism ; Tubulin/metabolism |
Chemical Substances | Angiogenic Proteins ; Carrier Proteins ; Cell Cycle Proteins ; SVBP protein, human ; Tubulin ; VASH1 protein, human ; VASH2 protein, human ; Calpain (EC 3.4.22.-) ; Calcium (SY7Q814VUP) |
Language | English |
Publishing date | 2022-05-06 |
Publishing country | England |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2993-2 |
ISSN | 1477-9137 ; 0021-9533 |
ISSN (online) | 1477-9137 |
ISSN | 0021-9533 |
DOI | 10.1242/jcs.259108 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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