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Analysis of GTPase-activating proteins: Rab1 and Rab43 are key Rabs required to maintain a functional Golgi complex in human cells
Abstract
Rab GTPases control vesicle movement and tethering membrane events in membrane trafficking. We used the 38 human Rab GTPase activating proteins (GAPs) to identify which of the 60 Rabs encoded in the human genome function at the Golgi complex. Surprisingly, this screen identified only two GAPs, RN-tre and TBC1D20, disrupting both Golgi organization and protein transport. RN-tre is the GAP for Rab43, and controls retrograde transport into the Golgi from the endocytic pathway. TBC1D20 is the ER-localized GAP for Rab1, and is the only GAP blocking the delivery of secretory cargo from the ER to the cell surface. Strikingly, its expression causes the loss of the Golgi complex, highlighting the importance of Rab1 for Golgi biogenesis. These effects can be antagonized by reticulon, a binding partner for TBC1D20 in the ER. Together, these findings indicate that Rab1 and Rab43 are key Rabs required for the biogenesis and maintenance of a functional Golgi structure, and suggest that other Rabs acting at the Golgi complex are likely to be functionally redundant.
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“Loss of RAB1A/B impaired secretion (Fig. 6d,e), serving as a positive control3637.”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [36]
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Self-citation
Metadata
- Authors
- Haas, A. K., Yoshimura, S.-I., Stephens, D. J., Preisinger, C., Fuchs, E., & Barr, F. A.
- Affiliations
- University of Liverpool (GB)
- University of Bristol (GB)
- Max Planck Institute of Biochemistry (DE)
- Corresponding author
- Barr, Francis A.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2007-09-01
- Volume
- 120
- Issue
- 17
- Pages
- 2997-3010
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2064782801
- Cited by
- 201
- References
- 56
- Citations by year
- 2025: 8 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 11 · 2020: 8 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 16 · 2015: 9 · 2014: 13 · 2013: 15 · 2012: 21
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- Rab GTPases, Rab1, Rab GTPase-activating protein, reticulons, retrograde transport, secretory pathway, ER-Golgi transport, membrane trafficking, functional redundancy
- MeSH terms
- rab11 GTP-Binding Proteins, Animals, Biological Transport, Endoplasmic Reticulum, Golgi Apparatus, HeLa Cells, Humans, Nerve Tissue Proteins, Phenotype, Recombinant Fusion Proteins, Genome, Human, rab GTP-Binding Proteins, rab1 GTP-Binding Proteins, Two-Hybrid System Techniques, RNA Interference
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