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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
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.
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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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