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

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 impo...

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Autores principales: Patel, Nishaben M., Siva, Meenakshi Sundaram Aravintha, Kumari, Ruchi, Shewale, Dipeshwari J., Rai, Ashim, Ritt, Michael, Sharma, Prerna, Setty, Subba Rao Gangi, Sivaramakrishnan, Sivaraj, Soppina, Virupakshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857691/
https://www.ncbi.nlm.nih.gov/pubmed/33536208
http://dx.doi.org/10.1126/sciadv.abd2054
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author Patel, Nishaben M.
Siva, Meenakshi Sundaram Aravintha
Kumari, Ruchi
Shewale, Dipeshwari J.
Rai, Ashim
Ritt, Michael
Sharma, Prerna
Setty, Subba Rao Gangi
Sivaramakrishnan, Sivaraj
Soppina, Virupakshi
author_facet Patel, Nishaben M.
Siva, Meenakshi Sundaram Aravintha
Kumari, Ruchi
Shewale, Dipeshwari J.
Rai, Ashim
Ritt, Michael
Sharma, Prerna
Setty, Subba Rao Gangi
Sivaramakrishnan, Sivaraj
Soppina, Virupakshi
author_sort Patel, Nishaben M.
collection PubMed
description 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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spelling pubmed-78576912021-02-16 KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell Patel, Nishaben M. Siva, Meenakshi Sundaram Aravintha Kumari, Ruchi Shewale, Dipeshwari J. Rai, Ashim Ritt, Michael Sharma, Prerna Setty, Subba Rao Gangi Sivaramakrishnan, Sivaraj Soppina, Virupakshi Sci Adv Research Articles 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. American Association for the Advancement of Science 2021-02-03 /pmc/articles/PMC7857691/ /pubmed/33536208 http://dx.doi.org/10.1126/sciadv.abd2054 Text en 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). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Patel, Nishaben M.
Siva, Meenakshi Sundaram Aravintha
Kumari, Ruchi
Shewale, Dipeshwari J.
Rai, Ashim
Ritt, Michael
Sharma, Prerna
Setty, Subba Rao Gangi
Sivaramakrishnan, Sivaraj
Soppina, Virupakshi
KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell
title KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell
title_full KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell
title_fullStr KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell
title_full_unstemmed KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell
title_short KIF13A motors are regulated by Rab22A to function as weak dimers inside the cell
title_sort kif13a motors are regulated by rab22a to function as weak dimers inside the cell
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857691/
https://www.ncbi.nlm.nih.gov/pubmed/33536208
http://dx.doi.org/10.1126/sciadv.abd2054
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