Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.

The ESCRT pathway is evolutionarily conserved across eukaryotes and plays key roles in a variety of membrane remodeling processes. A new Drosophila mutant recovered in our forward genetic screens for synaptic transmission mutants mapped to the vps24 gene encoding a subunit of the ESCRT-III complex....

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Autores principales:	Jonathan R Florian, Samuel J DeMatte, Devon M Sweeder, Richard W Ordway, Fumiko Kawasaki
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d82a566b20c540c8b49bc3694483e809
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spelling	oai:doaj.org-article:d82a566b20c540c8b49bc3694483e8092021-11-25T06:19:19ZGenetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.1932-620310.1371/journal.pone.0251184https://doaj.org/article/d82a566b20c540c8b49bc3694483e8092021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251184https://doaj.org/toc/1932-6203The ESCRT pathway is evolutionarily conserved across eukaryotes and plays key roles in a variety of membrane remodeling processes. A new Drosophila mutant recovered in our forward genetic screens for synaptic transmission mutants mapped to the vps24 gene encoding a subunit of the ESCRT-III complex. Molecular characterization indicated a loss of VPS24 function, however the mutant is viable and thus loss of VPS24 may be studied in a developed multicellular organism. The mutant exhibits deficits in locomotion and lifespan and, notably, these phenotypes are rescued by neuronal expression of wild-type VPS24. At the cellular level, neuronal and muscle cells exhibit marked expansion of a ubiquitin-positive lysosomal compartment, as well as accumulation of autophagic intermediates, and these phenotypes are rescued cell-autonomously. Moreover, VPS24 expression in glia suppressed the mutant phenotype in muscle, indicating a cell-nonautonomous function for VPS24 in protective intercellular signaling. Ultrastructural analysis of neurons and muscle indicated marked accumulation of the lysosomal compartment in the vps24 mutant. In the neuronal cell body, this included characteristic lysosomal structures associated with an expansive membrane compartment with a striking tubular network morphology. These findings further define the in vivo roles of VPS24 and the ESCRT pathway in lysosome homeostasis and their potential contributions to neurodegenerative diseases characterized by defective ESCRT or lysosome function.Jonathan R FlorianSamuel J DeMatteDevon M SweederRichard W OrdwayFumiko KawasakiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251184 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jonathan R Florian Samuel J DeMatte Devon M Sweeder Richard W Ordway Fumiko Kawasaki Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.
description	The ESCRT pathway is evolutionarily conserved across eukaryotes and plays key roles in a variety of membrane remodeling processes. A new Drosophila mutant recovered in our forward genetic screens for synaptic transmission mutants mapped to the vps24 gene encoding a subunit of the ESCRT-III complex. Molecular characterization indicated a loss of VPS24 function, however the mutant is viable and thus loss of VPS24 may be studied in a developed multicellular organism. The mutant exhibits deficits in locomotion and lifespan and, notably, these phenotypes are rescued by neuronal expression of wild-type VPS24. At the cellular level, neuronal and muscle cells exhibit marked expansion of a ubiquitin-positive lysosomal compartment, as well as accumulation of autophagic intermediates, and these phenotypes are rescued cell-autonomously. Moreover, VPS24 expression in glia suppressed the mutant phenotype in muscle, indicating a cell-nonautonomous function for VPS24 in protective intercellular signaling. Ultrastructural analysis of neurons and muscle indicated marked accumulation of the lysosomal compartment in the vps24 mutant. In the neuronal cell body, this included characteristic lysosomal structures associated with an expansive membrane compartment with a striking tubular network morphology. These findings further define the in vivo roles of VPS24 and the ESCRT pathway in lysosome homeostasis and their potential contributions to neurodegenerative diseases characterized by defective ESCRT or lysosome function.
format	article
author	Jonathan R Florian Samuel J DeMatte Devon M Sweeder Richard W Ordway Fumiko Kawasaki
author_facet	Jonathan R Florian Samuel J DeMatte Devon M Sweeder Richard W Ordway Fumiko Kawasaki
author_sort	Jonathan R Florian
title	Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.
title_short	Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.
title_full	Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.
title_fullStr	Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.
title_full_unstemmed	Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.
title_sort	genetic analysis of the drosophila escrt-iii complex protein, vps24, reveals a novel function in lysosome homeostasis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d82a566b20c540c8b49bc3694483e809
work_keys_str_mv	AT jonathanrflorian geneticanalysisofthedrosophilaescrtiiicomplexproteinvps24revealsanovelfunctioninlysosomehomeostasis AT samueljdematte geneticanalysisofthedrosophilaescrtiiicomplexproteinvps24revealsanovelfunctioninlysosomehomeostasis AT devonmsweeder geneticanalysisofthedrosophilaescrtiiicomplexproteinvps24revealsanovelfunctioninlysosomehomeostasis AT richardwordway geneticanalysisofthedrosophilaescrtiiicomplexproteinvps24revealsanovelfunctioninlysosomehomeostasis AT fumikokawasaki geneticanalysisofthedrosophilaescrtiiicomplexproteinvps24revealsanovelfunctioninlysosomehomeostasis
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Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.

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