Retinal degeneration in choroideremia: deficiency of rab geranylgeranyl transferase.
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.
Seabra
M C
MC
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Brown
M S
MS
Goldstein
J L
JL
D000328:Adult; D019883:Alkyl and Aryl Transferases; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002829:Choroid / Q000737:chemistry; D015794:Choroideremia / Q000235:genetics*; D005260:Female; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000737:chemistry; D010857:Pigment Epithelium of Eye / Q000737:chemistry; D017368:Protein Prenylation; D012160:Retina / Q000737:chemistry; D013379:Substrate Specificity; D014166:Transferases / Q000172:deficiency* / Q000235:genetics; D020761:rab1 GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins
D009419:Nerve Tissue Proteins; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C075607:Rab geranylgeranyltransferase; D019204:GTP-Binding Proteins; D020761:rab1 GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins