Cargando…
Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases
Neuronal autophagosomes, “self-eating” degradative organelles, form at presynaptic sites in the distal axon and are transported to the soma to recycle their cargo. During transit, autophagic vacuoles (AVs) mature through fusion with lysosomes to acquire the enzymes necessary to breakdown their cargo...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9901177/ https://www.ncbi.nlm.nih.gov/pubmed/36747648 http://dx.doi.org/10.1101/2023.01.28.526044 |
_version_ | 1784882988071256064 |
---|---|
author | Cason, Sydney E. Holzbaur, Erika L.F. |
author_facet | Cason, Sydney E. Holzbaur, Erika L.F. |
author_sort | Cason, Sydney E. |
collection | PubMed |
description | Neuronal autophagosomes, “self-eating” degradative organelles, form at presynaptic sites in the distal axon and are transported to the soma to recycle their cargo. During transit, autophagic vacuoles (AVs) mature through fusion with lysosomes to acquire the enzymes necessary to breakdown their cargo. AV transport is driven primarily by the microtubule motor cytoplasmic dynein in concert with dynactin and a series of activating adaptors that change depending on organelle maturation state. The transport of mature AVs is regulated by the scaffolding proteins JIP3 and JIP4, both of which activate dynein motility in vitro. AV transport is also regulated by ARF6 in a GTP-dependent fashion. While GTP-bound ARF6 promotes the formation of the JIP3/4-dynein-dynactin complex, RAB10 competes with the activity of this complex by increasing kinesin recruitment to axonal AVs and lysosomes. These interactions highlight the complex coordination of motors regulating organelle transport in neurons. |
format | Online Article Text |
id | pubmed-9901177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-99011772023-02-07 Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases Cason, Sydney E. Holzbaur, Erika L.F. bioRxiv Article Neuronal autophagosomes, “self-eating” degradative organelles, form at presynaptic sites in the distal axon and are transported to the soma to recycle their cargo. During transit, autophagic vacuoles (AVs) mature through fusion with lysosomes to acquire the enzymes necessary to breakdown their cargo. AV transport is driven primarily by the microtubule motor cytoplasmic dynein in concert with dynactin and a series of activating adaptors that change depending on organelle maturation state. The transport of mature AVs is regulated by the scaffolding proteins JIP3 and JIP4, both of which activate dynein motility in vitro. AV transport is also regulated by ARF6 in a GTP-dependent fashion. While GTP-bound ARF6 promotes the formation of the JIP3/4-dynein-dynactin complex, RAB10 competes with the activity of this complex by increasing kinesin recruitment to axonal AVs and lysosomes. These interactions highlight the complex coordination of motors regulating organelle transport in neurons. Cold Spring Harbor Laboratory 2023-01-29 /pmc/articles/PMC9901177/ /pubmed/36747648 http://dx.doi.org/10.1101/2023.01.28.526044 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Cason, Sydney E. Holzbaur, Erika L.F. Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases |
title | Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases |
title_full | Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases |
title_fullStr | Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases |
title_full_unstemmed | Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases |
title_short | Axonal transport of autophagosomes is regulated by dynein activators JIP3/JIP4 and ARF/RAB GTPases |
title_sort | axonal transport of autophagosomes is regulated by dynein activators jip3/jip4 and arf/rab gtpases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9901177/ https://www.ncbi.nlm.nih.gov/pubmed/36747648 http://dx.doi.org/10.1101/2023.01.28.526044 |
work_keys_str_mv | AT casonsydneye axonaltransportofautophagosomesisregulatedbydyneinactivatorsjip3jip4andarfrabgtpases AT holzbaurerikalf axonaltransportofautophagosomesisregulatedbydyneinactivatorsjip3jip4andarfrabgtpases |