Ras‐activated endocytosis is mediated by the Rab5 guanine nucleotide exchange activity of RIN1
Open accessAbstract
RIN1 was originally identified by its ability to inhibit activated Ras and likely participates in multiple signaling pathways because it binds c-ABL and 14-3-3 proteins, in addition to Ras. RIN1 also contains a region homologous to the catalytic domain of Vps9p-like Rab guanine nucleotide exchange factors (GEFs). Here, we show that this region is necessary and sufficient for RIN1 interaction with the GDP-bound Rabs, Vps21p, and Rab5A. RIN1 is also shown to stimulate Rab5 guanine nucleotide exchange, Rab5A-dependent endosome fusion, and EGF receptor-mediated endocytosis. The stimulatory effect of RIN1 on all three of these processes is potentiated by activated Ras. We conclude that Ras-activated endocytosis is facilitated, in part, by the ability of Ras to directly regulate the Rab5 nucleotide exchange activity of RIN1.
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RIN1 and PLD2 have been implicated in activating receptor-mediated endocytosis, RAB7B in late endosomes, and CD81 in exosomes and multivesicular bodies.
“For instance, RIN1 and PLD2 have been implicated in activating receptor‐mediated endocytosis, 31 , 32 RAB7B in late endosomes, 33 , 34 and CD81 in exosomes and multivesicular bodies (MVBs). 35”
From Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes (2025) · cites this paper as [31]
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Bar-Sagi, D., & Feramisco, J. R. (1986) · Science · doi:10.1126/science.3090687 · Cited by 734 · see citing works
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Tse, S. M. L., Furuya, W., Gold, E., Schreiber, A. D., Sandvig, K., Inman, R. D., & Grinstein, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m207966200 · Cited by 124 · see citing works
Protective mechanisms against Alzheimer's disease in APOE3‐Christchurch homozygous astrocytes
Tian, X., Rivera, E. K., Hwang, I., Nikitina, A. A., Smith, J. A., Cho, Y. J., Sala‐Jarque, J., DuBose, A., Andriola, C., Gollan‐Myers, T., et al. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70589 · Cited by 7 · see citing works
- Authors
- Tall, G. G., Barbieri, M. A., Stahl, P. D., & Horazdovsky, B. F.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Washington University in St. Louis (US)
- Corresponding author
- Horazdovsky, Bruce F.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2001-07
- Volume
- 1
- Issue
- 1
- Pages
- 73-82
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2142623337
- Cited by
- 308
- References
- 1
- Citations by year
- 2025: 10 · 2024: 6 · 2023: 5 · 2022: 9 · 2021: 5 · 2020: 9 · 2019: 6 · 2018: 8 · 2017: 8 · 2016: 10 · 2015: 14 · 2014: 9 · 2013: 17 · 2012: 29
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM 42259, GM-55301, R01GM042259, R01GM055301)
- National Institute of Allergy and Infectious Diseases (AI-35884, R01AI035884, AI-20015)
- 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
- RIN1, Rab5, Ras signaling, endocytosis, guanine nucleotide exchange factor, Rab5a, endosome fusion, EGF receptor
- MeSH terms
- Animals, Carrier Proteins, Endocytosis, Fibroblasts, Fungal Proteins, Cricetinae, Endosomes, Gene Expression, CHO Cells, ras Proteins, Catalytic Domain, Guanine Nucleotide Exchange Factors, rab GTP-Binding Proteins, rab5 GTP-Binding Proteins, Saccharomyces cerevisiae Proteins, Vesicular Transport Proteins, Intracellular Signaling Peptides and Proteins, Mice, In Vitro Techniques
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