期刊
SCIENCE ADVANCES
卷 7, 期 6, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd2054
关键词
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资金
- DBT [BT/PR15214/BRB/10/1449/2015, BT/RLF/re-entry/45/2015]
- DST-SERB [ECR/2016/000913]
- IIT Gandhinagar
- NIH [1R35GM126940-02]
- India Alliance [500122/Z/09/Z]
- SERB [CRG/2019/000281]
- DBT (NBACD-2019)
- IISc graduate fellowship
The research reveals the unique mechanism of KIF13A dimerization modulated by Rab22A during RE tubulation, leading to balanced motility and force against multiple dyneins in a molecular tug-of-war to regulate endocytic recycling and cellular homeostasis. This demonstrates that KIF13A motors are fine-tuned at a single-molecule level to function as weak dimers on cellular cargo.
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.
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