cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein

Douglas A. Andres; Miguel C. Seabra; Michael S. Brown; Scott A. Armstrong; Tor E. Smeland; Frans P.M. Cremers; Joseph L. Goldstein

doi:10.1016/0092-8674(93)90639-8

cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein

Douglas A. Andres, Miguel C. Seabra, Michael S. Brown, Scott A. Armstrong, Tor E. Smeland, Frans P.M. Cremers, Joseph L. Goldstein

Research output: Contribution to journal › Article › peer-review

300 Scopus citations

Abstract

cDNA cloning of component A of rat Rab geranylgeranyl transferase confirms identity of the protein with the human choroideremia gene product and its resemblance to Rab3A guanine nucleotide dissociation inhibitor (GDI), which binds prenylated Rabs. In biochemical assays we demonstrate that component A binds unprenylated Rab1A, presents it to the catalytic component B, and remains bound to it after the geranylgeranyl transfer reaction. In the absence of detergents, the reaction terminates when all of component A is occupied with prenylated Rab. Detergents allow multiple rounds of catalysis, apparently by dissociating the component A-Rab complex and thus allowing recycling of component A. Within the cell, component A may be regenerated by transferring its prenylated Rab to a protein acceptor, such as Rab3A GDI. In view of its function in escorting Rab proteins during and presumably after the prenyl transfer reaction, we propose to rename component A as Rab escort protein (REP). A genetic defect in REP underlies human choroideremia, a disease of retinal degeneration.

Original language	English
Pages (from-to)	1091-1099
Number of pages	9
Journal	Cell
Volume	73
Issue number	6
DOIs	https://doi.org/10.1016/0092-8674(93)90639-8
State	Published - Jun 18 1993

Bibliographical note

Funding Information:
We thank Thomas Siidhof for helpful comments; Richard Gibson and Veronica Martinez for excellent technical assistance; and Jeff Cormier for DNA sequencing. This research was supported by research grants from the National Institutes of Health (HL20946) and the Perot Family Foundation. D. A. A. is the recipient of a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Rs-search; M. C. S. is the recipient of a Fulbright Scholarship; S. A. A. is supported by Medical Scientists Training Grant GM06014. F. P. M. C. is the recipient of a sabbatical fellowship from the Royal Netherlands Academy of Arts and Sciences; his permanent address is at the Department of Human Genetics, University Hospital Nijmegen, 6506 HB Nijmegen, The Netherlands.

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology (all)

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10.1016/0092-8674(93)90639-8

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title = "cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein",

abstract = "cDNA cloning of component A of rat Rab geranylgeranyl transferase confirms identity of the protein with the human choroideremia gene product and its resemblance to Rab3A guanine nucleotide dissociation inhibitor (GDI), which binds prenylated Rabs. In biochemical assays we demonstrate that component A binds unprenylated Rab1A, presents it to the catalytic component B, and remains bound to it after the geranylgeranyl transfer reaction. In the absence of detergents, the reaction terminates when all of component A is occupied with prenylated Rab. Detergents allow multiple rounds of catalysis, apparently by dissociating the component A-Rab complex and thus allowing recycling of component A. Within the cell, component A may be regenerated by transferring its prenylated Rab to a protein acceptor, such as Rab3A GDI. In view of its function in escorting Rab proteins during and presumably after the prenyl transfer reaction, we propose to rename component A as Rab escort protein (REP). A genetic defect in REP underlies human choroideremia, a disease of retinal degeneration.",

author = "Andres, {Douglas A.} and Seabra, {Miguel C.} and Brown, {Michael S.} and Armstrong, {Scott A.} and Smeland, {Tor E.} and Cremers, {Frans P.M.} and Goldstein, {Joseph L.}",

note = "Funding Information: We thank Thomas Siidhof for helpful comments; Richard Gibson and Veronica Martinez for excellent technical assistance; and Jeff Cormier for DNA sequencing. This research was supported by research grants from the National Institutes of Health (HL20946) and the Perot Family Foundation. D. A. A. is the recipient of a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Rs-search; M. C. S. is the recipient of a Fulbright Scholarship; S. A. A. is supported by Medical Scientists Training Grant GM06014. F. P. M. C. is the recipient of a sabbatical fellowship from the Royal Netherlands Academy of Arts and Sciences; his permanent address is at the Department of Human Genetics, University Hospital Nijmegen, 6506 HB Nijmegen, The Netherlands.",

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T1 - cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein

AU - Andres, Douglas A.

AU - Seabra, Miguel C.

AU - Brown, Michael S.

AU - Armstrong, Scott A.

AU - Smeland, Tor E.

AU - Cremers, Frans P.M.

AU - Goldstein, Joseph L.

N1 - Funding Information: We thank Thomas Siidhof for helpful comments; Richard Gibson and Veronica Martinez for excellent technical assistance; and Jeff Cormier for DNA sequencing. This research was supported by research grants from the National Institutes of Health (HL20946) and the Perot Family Foundation. D. A. A. is the recipient of a postdoctoral fellowship from the Jane Coffin Childs Memorial Fund for Medical Rs-search; M. C. S. is the recipient of a Fulbright Scholarship; S. A. A. is supported by Medical Scientists Training Grant GM06014. F. P. M. C. is the recipient of a sabbatical fellowship from the Royal Netherlands Academy of Arts and Sciences; his permanent address is at the Department of Human Genetics, University Hospital Nijmegen, 6506 HB Nijmegen, The Netherlands.

PY - 1993/6/18

Y1 - 1993/6/18

N2 - cDNA cloning of component A of rat Rab geranylgeranyl transferase confirms identity of the protein with the human choroideremia gene product and its resemblance to Rab3A guanine nucleotide dissociation inhibitor (GDI), which binds prenylated Rabs. In biochemical assays we demonstrate that component A binds unprenylated Rab1A, presents it to the catalytic component B, and remains bound to it after the geranylgeranyl transfer reaction. In the absence of detergents, the reaction terminates when all of component A is occupied with prenylated Rab. Detergents allow multiple rounds of catalysis, apparently by dissociating the component A-Rab complex and thus allowing recycling of component A. Within the cell, component A may be regenerated by transferring its prenylated Rab to a protein acceptor, such as Rab3A GDI. In view of its function in escorting Rab proteins during and presumably after the prenyl transfer reaction, we propose to rename component A as Rab escort protein (REP). A genetic defect in REP underlies human choroideremia, a disease of retinal degeneration.

AB - cDNA cloning of component A of rat Rab geranylgeranyl transferase confirms identity of the protein with the human choroideremia gene product and its resemblance to Rab3A guanine nucleotide dissociation inhibitor (GDI), which binds prenylated Rabs. In biochemical assays we demonstrate that component A binds unprenylated Rab1A, presents it to the catalytic component B, and remains bound to it after the geranylgeranyl transfer reaction. In the absence of detergents, the reaction terminates when all of component A is occupied with prenylated Rab. Detergents allow multiple rounds of catalysis, apparently by dissociating the component A-Rab complex and thus allowing recycling of component A. Within the cell, component A may be regenerated by transferring its prenylated Rab to a protein acceptor, such as Rab3A GDI. In view of its function in escorting Rab proteins during and presumably after the prenyl transfer reaction, we propose to rename component A as Rab escort protein (REP). A genetic defect in REP underlies human choroideremia, a disease of retinal degeneration.

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cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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