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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Abstract
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 |
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| 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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