Retinal degeneration in choroideremia: deficiency of rab geranylgeranyl transferase
Abstract
Rab geranylgeranyl transferase (GG transferase) is a two-component enzyme that attaches 20-carbon isoprenoid groups to cysteine residues in Rab proteins, a family of guanosine triphosphate-binding proteins that regulate vesicular traffic. The mutant gene in human choroideremia, an X-linked form of retinal degeneration, encodes a protein that resembles component A of rat Rab GG transferase. Lymphoblasts from choroideremia subjects showed a marked deficiency in the activity of component A, but not component B, of Rab GG transferase. The deficiency was more pronounced when the substrate was Rab3A, a synaptic vesicle protein, than it was when the substrate was Rab1A, a protein of the endoplasmic reticulum. The data imply the existence of multiple component A proteins, one of which is missing in choroideremia.
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REP1 facilitates isoprenyl modifications of RAB GTPases and is encoded by the CHM gene, which is mutant in the retinal degeneration choroideremia.
“REP1 facilitates isoprenyl modifications of RAB GTPases and is encoded by the CHM gene, which is mutant in the retinal degeneration choroideremia (Seabra et al., 1993).”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Seabra et al., 1993
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- Authors
- Seabra, M. C., Brown, M. S., & Goldstein, J. L.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Venue
- Science
- Published
- 1993-01-15
- Volume
- 259
- Issue
- 5093
- Pages
- 377-381
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2000072353
- Cited by
- 337
- References
- 27
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 8 · 2021: 13 · 2020: 16 · 2019: 15 · 2018: 12 · 2017: 13 · 2016: 8 · 2015: 9 · 2014: 12 · 2013: 7 · 2012: 5
- FWCI
- 10.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-20948, P01HL020948)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- choroideremia, retinal degeneration, Rab3A, Rab1A, isoprenoid modification, X-linked inheritance, vesicle trafficking, lymphoblasts
- MeSH terms
- Adult, Cell Line, Transformed, Cells, Cultured, Choroid, Female, Humans, Lymphocyte Activation, Male, Middle Aged, Mutation, Nerve Tissue Proteins, Photoreceptor Cells, Pigment Epithelium of Eye, Retina, Substrate Specificity, Transferases, Choroideremia, Gene Expression Regulation, Enzymologic, Protein Prenylation, GTP-Binding Proteins, Alkyl and Aryl Transferases, rab3 GTP-Binding Proteins, rab1 GTP-Binding Proteins
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