ArticleThe Journal of biological chemistry2023
Targeting of the Mon1-Ccz1 Rab guanine nucleotide exchange factor to distinct organelles by a synergistic protein and lipid code.
Article in The Journal of biological chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- The planar cell polarity protein Vangl2 interacts with the PDZ-domains of Scribble but not with a unique PDZ-like domain in Inturned.FEBS letters · 2026Article
- Retromer mediates Ypt7-dependent lipid droplet internalization.Cell reports · 2026Article
- Endosomal maturation is controlled by the trimeric Bulli-Mon1-Ccz1 Rab7 GEF complex and the Rab5 GTPase-activating protein GAPsec.Journal of cell science · 2026Article
- Barley powdery mildew effector CSEP0162 interacts with the endosome membrane-binding domain of barley MON1.Journal of experimental botany · 2025Article
- Cryo-EM structure of the human MON1A-CCZ1-RAB7A complex provides insights into nucleotide exchange mechanism.Life metabolism · 2025Article
- Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned.Science advances · 2025Article
- ESCRTing the RABs through conversion.Biochemical Society transactions · 2025Review
- A comparative analysis of paxillin and Hic-5 proximity interactomes.Cytoskeleton (Hoboken, N.J.) · 2025Article
- Hemifusomes and Interacting Proteolipid Nanodroplets Mediate Multi-Vesicular Body Formation.Research square · 2024Article
- Structure of the endosomal CORVET tethering complex.Nature communications · 2024Article
- The GTPase activating protein Gyp7 regulates Rab7/Ypt7 activity on late endosomes.The Journal of cell biology · 2024Article
- Loss of the HOPS complex disrupts early-to-late endosome transition, impairs endosomal recycling and induces accumulation of amphisomes.Molecular biology of the cell · 2024Article
- Regulatory sites in the Mon1-Ccz1 complex control Rab5 to Rab7 transition and endosome maturation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structure of the metazoan Rab7 GEF complex Mon1-Ccz1-Bulli.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the small GTPase Rab7 by its cognate guanine nucleotide exchange factor Mon1-Ccz1 (MC1) is a key step in the maturation of endosomes and autophagosomes. This process is tightly regulated and subject to precise spatiotemporal control of MC1 localization, but the mechanisms that underly MC1 localization have not been fully elucidated. We here identify and characterize an amphipathic helix in Ccz1, which is required for the function of Mon-Ccz1 in autophagy, but not endosomal maturation. Furthermore, our data show that the interaction of the Ccz1 amphipathic helix with lipid packing defects, binding of Mon1 basic patches to positively charged lipids, and association of MC1 with recruiter proteins collectively govern membrane recruitment of the complex in a synergistic and redundant manner. Membrane binding enhances MC1 activity predominantly by increasing enzyme and substrate concentration on the membrane, but interaction with recruiter proteins can further stimulate the guanine nucleotide exchange factor. Our data demonstrate that specific protein and lipid cues convey the differential targeting of MC1 to endosomes and autophagosomes. In conclusion, we reveal the molecular basis for how MC1 is adapted to recognize distinct target compartments by exploiting the unique biophysical properties of organelle membranes and thus provide a model for how the complex is regulated and activated independently in different functional contexts.
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