Kumari, Amrita and Kumar, Chandan and Pergu, Rajaiah and Kumar, Megha and Mahale, Sagar P. and Wasnik, Neeraj and Mylavarapu, Sivaram V.S. (2021) Phosphorylation and Pin1 binding to the LIC1 subunit selectively regulate mitotic dynein functions. Journal of Cell Biology, 220 (12). ISSN 0021-9525

Text Phosphorylation and Pin1 binding to the LIC1 subunit selectively regulate mitotic dynein functions.bibtex Restricted to Repository staff only Download (1902b) | Request a copy

Abstract

The dynein motor performs multiple functions in mitosis by engaging with a wide cargo spectrum. One way to regulate dynein’s cargo-binding selectivity is through the C-terminal domain (CTD) of its light intermediate chain 1 subunit (LIC1), which binds directly with cargo adaptors. Here we show that mitotic phosphorylation of LIC1-CTD at its three cdk1 sites is required for proper mitotic progression, for dynein loading onto prometaphase kinetochores, and for spindle assembly checkpoint inactivation in human cells. Mitotic LIC1-CTD phosphorylation also engages the prolyl isomerase Pin1 predominantly to Hook2-dynein-Nde1-Lis1 complexes, but not to dynein-spindly-dynactin complexes. LIC1-CTD dephosphorylation abrogates dynein-Pin1 binding, promotes prophase centrosome–nuclear envelope detachment, and impairs metaphase chromosome congression and mitotic Golgi fragmentation, without affecting interphase membrane transport. Phosphomutation of a conserved LIC1-CTD SP site in zebrafish leads to early developmental defects. Our work reveals that LIC1-CTD phosphorylation differentially regulates distinct mitotic dynein pools and suggests the evolutionary conservation of this phosphoregulation.

Item Type:	Article
Subjects:	Biomedical Science Biochemical and Biophysical Sciences
Depositing User:	RCB Library
Date Deposited:	10 Jan 2022 07:12
Last Modified:	10 Jan 2022 07:12
URI:	http://rcb.sciencecentral.in/id/eprint/664

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