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The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein
Garner, Kirsten E.L. Salter, Anna Lau, Clinton K. Gurusaran, Manickam Villemant, Cécile M. Granger, Elizabeth P. Woodman, Philip G. Davies, Owen R. Burke, Brian E.
Garner, Kirsten E.L.
Salter, Anna
Lau, Clinton K.
Gurusaran, Manickam
Villemant, Cécile M.
Granger, Elizabeth P.
Woodman, Philip G.
Davies, Owen R.
Burke, Brian E.
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Epub Date
Issue Date
2023-03-22
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Abstract
Cytoplasmic dynein-driven movement of chromosomes during prophase I of mammalian meiosis is essential for synapsis and genetic exchange. Dynein connects to chromosome telomeres via KASH5 and SUN1 or SUN2, which together span the nuclear envelope. Here, we show that KASH5 promotes dynein motility in vitro, and cytosolic KASH5 inhibits dynein’s interphase functions. KASH5 interacts with a dynein light intermediate chain (DYNC1LI1 or DYNC1LI2) via a conserved helix in the LIC C-terminal, and this region is also needed for dynein’s recruitment to other cellular membranes. KASH5’s N-terminal EF-hands are essential as the interaction with dynein is disrupted by mutation of key calcium-binding residues, although it is not regulated by cellular calcium levels. Dynein can be recruited to KASH5 at the nuclear envelope independently of dynactin, while LIS1 is essential for dynactin incorporation into the KASH5–dynein complex. Altogether, we show that the transmembrane protein KASH5 is an activating adaptor for dynein and shed light on the hierarchy of assembly of KASH5–dynein–dynactin complexes.
Citation
Garner, K.E.L., Salter, A., Lau, C.K. et al. (2023) The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein. Journal of Cell Biology, 222 (5): e202204042.
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Research Unit
PubMed ID
36946995 (pubmed)
PubMed Central ID
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Journal article
Language
en
Description
©2023 The Authors. Published by Rockefeller University Press. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link: https://doi.org/10.1083/jcb.202204042
Series/Report no.
ISSN
0021-9525
EISSN
1540-8140
ISBN
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Sponsors
The work in V. Allan’s laboratory was funded by the Biotechnology and Biological Sciences Research Council (BB/N006933/1 and a Ph.D. studentship to E. Granger), the Medical Research Council (Ph.D. studentship to C. Villemant), and the University of Manchester. A. Salter was funded by the University of Manchester-A*STAR Research Attachment Programme (ARAP). The work in B. Burke’s laboratory was funded by the Singapore Biomedical Research Council and the Singapore Agency for Science Technology and Research, A*STAR. O. Davies is funded by a Wellcome Senior Research Fellowship (grant number 219413/Z/19/Z). C. Lau was funded by grants from the Wellcome Trust (WT210711) and the Medical Research Council, UK (MC_UP_A025_1011), awarded to Dr. Andrew Carter.
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Licence for published version: Creative Commons Attribution 4.0 International