The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor
- University of Michigan-Ann Arbor, United States
- University of Gothenburg, Sweden
Abstract
Dynein harnesses ATP hydrolysis to move cargo on microtubules in multiple biological contexts. Dynein meets a unique challenge in meiosis by moving chromosomes tethered to the nuclear envelope to facilitate homolog pairing essential for gametogenesis. Though processive dynein motility requires binding to an activating adaptor, the identity of the activating adaptor required for dynein to move meiotic chromosomes is unknown. We show that the meiosis-specific nuclear-envelope protein KASH5 is a dynein activating adaptor: KASH5 directly binds dynein using a mechanism conserved among activating adaptors and converts dynein into a processive motor. We map the dynein-binding surface of KASH5, identifying mutations that abrogate dynein binding in vitro and disrupt recruitment of the dynein machinery to the nuclear envelope in cultured cells and mouse spermatocytes in vivo. Our study identifies KASH5 as the first transmembrane dynein activating adaptor and provides molecular insights into how it activates dynein during meiosis.
Data availability
Source data for TIRF experiments in Figure 3-6 are found in the file "Agrawal_etal_Source data" and labeled appropriately.All custom macros written for this study (used in Figure 5) are available on GitHub (https://github.com/DeSantis-Lab/Nuclear_Envelope_Localization_Macros)
Article and author information
Author details
Funding
National Institutes of Health (R00-GM127757)
- Morgan E DeSantis
National Institutes of Health (R01-GM120094)
- Jayakrishnan Nandakumar
American Heart Association (RSG-17-037-01-DMC)
- Jayakrishnan Nandakumar
European Research Council (StG-801659)
- Hiroki Shibuya
Swedish Research Council (2018-03426)
- Hiroki Shibuya
Knut och Alice Wallenbergs Stiftelse (KAW2019.0180)
- Hiroki Shibuya
American Heart Association
- Ritvija Agrawal
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ahmet Yildiz, University of California, Berkeley, United States
Ethics
Animal experimentation: All animal experiments were approved by and performed in compliance with the regulations at the University of Gothenburg Institutional Animal Care and Use Committee (#1316/18).
Version history
- Received: February 26, 2022
- Preprint posted: March 12, 2022 (view preprint)
- Accepted: June 14, 2022
- Accepted Manuscript published: June 15, 2022 (version 1)
- Version of Record published: June 29, 2022 (version 2)
Copyright
© 2022, Agrawal et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor
eLife 11:e78201.
https://doi.org/10.7554/eLife.78201
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