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KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell

Patel, NM and Siva, MSA and Kumari, R and Shewale, DJ and Rai, A and Ritt, M and Sharma, P and Setty, SRG and Sivaramakrishnan, S and Soppina, V (2021) KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell. In: Science Advances, 7 (6).

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Official URL: https://doi.org/10.1126/sciadv.abd2054


Endocytic recycling is a complex itinerary, critical for many cellular processes. Membrane tubulation is a hallmark of recycling endosomes (REs), mediated by KIF13A, a kinesin-3 family motor. Understanding the regulatory mechanism of KIF13A in RE tubulation and cargo recycling is of fundamental importance but is overlooked. Here, we report a unique mechanism of KIF13A dimerization modulated by Rab22A, a small guanosine triphosphatase, during RE tubulation. A conserved proline between neck coil-coiled-coil (NC-CC1) domains of KIF13A creates steric hindrance, rendering the motors as inactive monomers. Rab22A plays an unusual role by binding to NC-CC1 domains of KIF13A, relieving proline-mediated inhibition and facilitating motor dimerization. As a result, KIF13A motors produce balanced motility and force against multiple dyneins in a molecular tug-of-war to regulate RE tubulation and homeostasis. Together, our findings demonstrate that KIF13A motors are tuned at a single-molecule level to function as weak dimers on the cellular cargo. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Item Type: Journal Article
Publication: Science Advances
Publisher: American Association for the Advancement of Science
Additional Information: The copyright of this article belongs to the authors.
Keywords: Dimerization; Recycling, Cellular process; Endocytic recycling; Guanosine triphosphatase; Recycling endosomes; Regulatory mechanism; Single molecule level; Steric hindrances; Tug of war (ToW), Dimers
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 16 Mar 2021 07:45
Last Modified: 16 Mar 2021 07:46
URI: http://eprints.iisc.ac.in/id/eprint/68195

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