This Is the End: Regulation of Rab7 Nucleotide Binding in Endolysosomal Trafficking and Autophagy

Rab7 – or in yeast, Ypt7p – governs membrane trafficking in the late endocytic and autophagic pathways. Rab7 also regulates mitochondrion-lysosome contacts, the sites of mitochondrial fission. Like all Rab GTPases, Rab7 cycles between an “active” GTP-bound form that binds downstream effectors – e.g....

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Main Author: Christopher Stroupe
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-10-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcell.2018.00129/full
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author Christopher Stroupe
author_facet Christopher Stroupe
author_sort Christopher Stroupe
collection DOAJ
description Rab7 – or in yeast, Ypt7p – governs membrane trafficking in the late endocytic and autophagic pathways. Rab7 also regulates mitochondrion-lysosome contacts, the sites of mitochondrial fission. Like all Rab GTPases, Rab7 cycles between an “active” GTP-bound form that binds downstream effectors – e.g., the HOPS and retromer complexes and the dynactin-binding Rab-interacting lysosomal protein (RILP) – and an “inactive” GDP-bound form that cannot bind effectors. Accessory proteins regulate the nucleotide binding state of Rab7: guanine nucleotide exchange factors (GEFs) stimulate exchange of bound GDP for GTP, resulting in Rab7 activation, whereas GTPase activating proteins (GAPs) boost Rab7’s GTP hydrolysis activity, thereby inactivating Rab7. This review will discuss the GEF and GAPs that control Rab7 nucleotide binding, and thus regulate Rab7’s activity in endolysosomal trafficking and autophagy. It will also consider how bacterial pathogens manipulate Rab7 nucleotide binding to support intracellular invasion and immune evasion.
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spelling doaj.art-e7432f7cb55d425ea027b0db713f616c2022-12-22T00:33:08ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2018-10-01610.3389/fcell.2018.00129408487This Is the End: Regulation of Rab7 Nucleotide Binding in Endolysosomal Trafficking and AutophagyChristopher StroupeRab7 – or in yeast, Ypt7p – governs membrane trafficking in the late endocytic and autophagic pathways. Rab7 also regulates mitochondrion-lysosome contacts, the sites of mitochondrial fission. Like all Rab GTPases, Rab7 cycles between an “active” GTP-bound form that binds downstream effectors – e.g., the HOPS and retromer complexes and the dynactin-binding Rab-interacting lysosomal protein (RILP) – and an “inactive” GDP-bound form that cannot bind effectors. Accessory proteins regulate the nucleotide binding state of Rab7: guanine nucleotide exchange factors (GEFs) stimulate exchange of bound GDP for GTP, resulting in Rab7 activation, whereas GTPase activating proteins (GAPs) boost Rab7’s GTP hydrolysis activity, thereby inactivating Rab7. This review will discuss the GEF and GAPs that control Rab7 nucleotide binding, and thus regulate Rab7’s activity in endolysosomal trafficking and autophagy. It will also consider how bacterial pathogens manipulate Rab7 nucleotide binding to support intracellular invasion and immune evasion.https://www.frontiersin.org/article/10.3389/fcell.2018.00129/fullRab GTPaseRab7Ypt7pguanine nucleotide exchange factorGEFGTPase-activating protein
spellingShingle Christopher Stroupe
This Is the End: Regulation of Rab7 Nucleotide Binding in Endolysosomal Trafficking and Autophagy
Frontiers in Cell and Developmental Biology
Rab GTPase
Rab7
Ypt7p
guanine nucleotide exchange factor
GEF
GTPase-activating protein
title This Is the End: Regulation of Rab7 Nucleotide Binding in Endolysosomal Trafficking and Autophagy
title_full This Is the End: Regulation of Rab7 Nucleotide Binding in Endolysosomal Trafficking and Autophagy
title_fullStr This Is the End: Regulation of Rab7 Nucleotide Binding in Endolysosomal Trafficking and Autophagy
title_full_unstemmed This Is the End: Regulation of Rab7 Nucleotide Binding in Endolysosomal Trafficking and Autophagy
title_short This Is the End: Regulation of Rab7 Nucleotide Binding in Endolysosomal Trafficking and Autophagy
title_sort this is the end regulation of rab7 nucleotide binding in endolysosomal trafficking and autophagy
topic Rab GTPase
Rab7
Ypt7p
guanine nucleotide exchange factor
GEF
GTPase-activating protein
url https://www.frontiersin.org/article/10.3389/fcell.2018.00129/full
work_keys_str_mv AT christopherstroupe thisistheendregulationofrab7nucleotidebindinginendolysosomaltraffickingandautophagy