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JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport
The MAP kinase and motor scaffold JIP3 prevents excess lysosome accumulation in axons of vertebrates and invertebrates. How JIP3’s interaction with dynein and kinesin-1 contributes to organelle clearance is unclear. We show that human dynein light intermediate chain (DLIC) binds the N-terminal RH1 d...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284427/ https://www.ncbi.nlm.nih.gov/pubmed/35829703 http://dx.doi.org/10.1083/jcb.202110057 |
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author | Celestino, Ricardo Gama, José B. Castro-Rodrigues, Artur F. Barbosa, Daniel J. Rocha, Helder d’Amico, Ennio A. Musacchio, Andrea Carvalho, Ana Xavier Morais-Cabral, João H. Gassmann, Reto |
author_facet | Celestino, Ricardo Gama, José B. Castro-Rodrigues, Artur F. Barbosa, Daniel J. Rocha, Helder d’Amico, Ennio A. Musacchio, Andrea Carvalho, Ana Xavier Morais-Cabral, João H. Gassmann, Reto |
author_sort | Celestino, Ricardo |
collection | PubMed |
description | The MAP kinase and motor scaffold JIP3 prevents excess lysosome accumulation in axons of vertebrates and invertebrates. How JIP3’s interaction with dynein and kinesin-1 contributes to organelle clearance is unclear. We show that human dynein light intermediate chain (DLIC) binds the N-terminal RH1 domain of JIP3, its paralog JIP4, and the lysosomal adaptor RILP. A point mutation in RH1 abrogates DLIC binding without perturbing the interaction between JIP3’s RH1 domain and kinesin heavy chain. Characterization of this separation-of-function mutation in Caenorhabditis elegans shows that JIP3–bound dynein is required for organelle clearance in the anterior process of touch receptor neurons. Unlike JIP3 null mutants, JIP3 that cannot bind DLIC causes prominent accumulation of endo-lysosomal organelles at the neurite tip, which is rescued by a disease-associated point mutation in JIP3’s leucine zipper that abrogates kinesin light chain binding. These results highlight that RH1 domains are interaction hubs for cytoskeletal motors and suggest that JIP3–bound dynein and kinesin-1 participate in bidirectional organelle transport. |
format | Online Article Text |
id | pubmed-9284427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-92844272023-01-13 JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport Celestino, Ricardo Gama, José B. Castro-Rodrigues, Artur F. Barbosa, Daniel J. Rocha, Helder d’Amico, Ennio A. Musacchio, Andrea Carvalho, Ana Xavier Morais-Cabral, João H. Gassmann, Reto J Cell Biol Article The MAP kinase and motor scaffold JIP3 prevents excess lysosome accumulation in axons of vertebrates and invertebrates. How JIP3’s interaction with dynein and kinesin-1 contributes to organelle clearance is unclear. We show that human dynein light intermediate chain (DLIC) binds the N-terminal RH1 domain of JIP3, its paralog JIP4, and the lysosomal adaptor RILP. A point mutation in RH1 abrogates DLIC binding without perturbing the interaction between JIP3’s RH1 domain and kinesin heavy chain. Characterization of this separation-of-function mutation in Caenorhabditis elegans shows that JIP3–bound dynein is required for organelle clearance in the anterior process of touch receptor neurons. Unlike JIP3 null mutants, JIP3 that cannot bind DLIC causes prominent accumulation of endo-lysosomal organelles at the neurite tip, which is rescued by a disease-associated point mutation in JIP3’s leucine zipper that abrogates kinesin light chain binding. These results highlight that RH1 domains are interaction hubs for cytoskeletal motors and suggest that JIP3–bound dynein and kinesin-1 participate in bidirectional organelle transport. Rockefeller University Press 2022-07-13 /pmc/articles/PMC9284427/ /pubmed/35829703 http://dx.doi.org/10.1083/jcb.202110057 Text en © 2022 Celestino et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Celestino, Ricardo Gama, José B. Castro-Rodrigues, Artur F. Barbosa, Daniel J. Rocha, Helder d’Amico, Ennio A. Musacchio, Andrea Carvalho, Ana Xavier Morais-Cabral, João H. Gassmann, Reto JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport |
title | JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport |
title_full | JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport |
title_fullStr | JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport |
title_full_unstemmed | JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport |
title_short | JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport |
title_sort | jip3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284427/ https://www.ncbi.nlm.nih.gov/pubmed/35829703 http://dx.doi.org/10.1083/jcb.202110057 |
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