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JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport

Authors :
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
d’Amico, Ennio A.
Source :
Journal of Cell Biology. 221
Publication Year :
2022
Publisher :
Rockefeller University Press, 2022.

Abstract

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.

Details

ISSN :
15408140 and 00219525
Volume :
221
Database :
OpenAIRE
Journal :
Journal of Cell Biology
Accession number :
edsair.doi.dedup.....0f6a0f2b2bd22c49dfe1e8727e261083
Full Text :
https://doi.org/10.1083/jcb.202110057