Who's in control? Principles of Rab GTPase activation in endolysosomal membrane trafficking and beyond

The eukaryotic endomembrane system consists of multiple interconnected organelles. Rab GTPases are organelle-specific markers that give identity to these membranes by recruiting transport and trafficking proteins. During transport processes or along organelle maturation, one Rab is replaced by anoth...

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Bibliographic Details
Published in:The Journal of cell biology Vol. 220; no. 9
Main Authors: Borchers, Ann-Christin, Langemeyer, Lars, Ungermann, Christian
Format: Journal Article
Language:English
Published: United States 06.09.2021
Subjects:
Animals
Autophagosomes - genetics
Autophagosomes - metabolism
Biological Transport
Cell Membrane - genetics
Cell Membrane - metabolism
Conserved Sequence
Endosomes - genetics
Endosomes - metabolism
Gene Expression Regulation
Guanine Nucleotide Exchange Factors - genetics
Guanine Nucleotide Exchange Factors - metabolism
Humans
Lysosomes - genetics
Lysosomes - metabolism
Organelle Biogenesis
rab GTP-Binding Proteins - genetics
rab GTP-Binding Proteins - metabolism
rab5 GTP-Binding Proteins - genetics
rab5 GTP-Binding Proteins - metabolism
rab7 GTP-Binding Proteins
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - metabolism
Signal Transduction
Vesicular Transport Proteins - genetics
Vesicular Transport Proteins - metabolism
ISSN:1540-8140, 1540-8140
Online Access:Get more information
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Summary:The eukaryotic endomembrane system consists of multiple interconnected organelles. Rab GTPases are organelle-specific markers that give identity to these membranes by recruiting transport and trafficking proteins. During transport processes or along organelle maturation, one Rab is replaced by another, a process termed Rab cascade, which requires at its center a Rab-specific guanine nucleotide exchange factor (GEF). The endolysosomal system serves here as a prime example for a Rab cascade. Along with endosomal maturation, the endosomal Rab5 recruits and activates the Rab7-specific GEF Mon1-Ccz1, resulting in Rab7 activation on endosomes and subsequent fusion of endosomes with lysosomes. In this review, we focus on the current idea of Mon1-Ccz1 recruitment and activation in the endolysosomal and autophagic pathway. We compare identified principles to other GTPase cascades on endomembranes, highlight the importance of regulation, and evaluate in this context the strength and relevance of recent developments in in vitro analyses to understand the underlying foundation of organelle biogenesis and maturation.
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ISSN:1540-8140
1540-8140
DOI:10.1083/jcb.202105120