Phosphorylation and Pin1 binding to the LIC1 subunit selectively regulate mitotic dynein functions.

Autor:	Kumari A; Laboratory of Cellular Dynamics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, third Milestone Faridabad-Gurgaon Expressway, Faridabad Haryana, India.; Manipal Academy of Higher Education, Manipal Karnataka, India., Kumar C; Laboratory of Cellular Dynamics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, third Milestone Faridabad-Gurgaon Expressway, Faridabad Haryana, India., Pergu R; Laboratory of Cellular Dynamics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, third Milestone Faridabad-Gurgaon Expressway, Faridabad Haryana, India.; Manipal Academy of Higher Education, Manipal Karnataka, India., Kumar M; Laboratory of Cellular Dynamics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, third Milestone Faridabad-Gurgaon Expressway, Faridabad Haryana, India.; Council of Scientific and Industrial Research, Centre for Cellular and Molecular Biology, Habsiguda, Hyderabad, Telangana, India.; Academy of Scientific and Innovative Research, New Delhi, India., Mahale SP; Laboratory of Cellular Dynamics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, third Milestone Faridabad-Gurgaon Expressway, Faridabad Haryana, India.; Manipal Academy of Higher Education, Manipal Karnataka, India., Wasnik N; Laboratory of Cellular Dynamics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, third Milestone Faridabad-Gurgaon Expressway, Faridabad Haryana, India., Mylavarapu SVS; Laboratory of Cellular Dynamics, Regional Centre for Biotechnology, NCR Biotech Science Cluster, third Milestone Faridabad-Gurgaon Expressway, Faridabad Haryana, India.; Manipal Academy of Higher Education, Manipal Karnataka, India.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2021 Dec 06; Vol. 220 (12). Date of Electronic Publication: 2021 Oct 28.
DOI:	10.1083/jcb.202005184
Abstrakt:	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. (© 2021 Kumari et al.)
Databáze:	MEDLINE
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