RGMs (repulsive guidance molecules) comprise a recently discovered family of GPI (glycosylphosphatidylinositol)-linked cell-membrane-associated proteins found in most vertebrate species. The three proteins, RGMa, RGMb and RGMc, products of distinct single-copy genes that arose early in vertebrate evolution, are ∼40–50% identical to each other in primary amino acid sequence, and share similarities in predicted protein domains and overall structure, as inferred by ab initio molecular modelling; yet the respective proteins appear to undergo distinct biosynthetic and processing steps, whose regulation has not been characterized to date. Each RGM also displays a discrete tissue-specific pattern of gene and protein expression, and each is proposed to have unique biological functions, ranging from axonal guidance during development (RGMa) to regulation of systemic iron metabolism (RGMc). All three RGM proteins appear capable of binding selected BMPs (bone morphogenetic proteins), and interactions with BMPs mediate at least some of the biological effects of RGMc on iron metabolism, but to date no role for BMPs has been defined in the actions of RGMa or RGMb. RGMa and RGMc have been shown to bind to the transmembrane protein neogenin, which acts as a critical receptor to mediate the biological effects of RGMa on repulsive axonal guidance and on neuronal survival, but its role in the actions of RGMc remains to be elucidated. Similarly, the full spectrum of biological functions of the three RGMs has not been completely characterized yet, and will remain an active topic of ongoing investigation.
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September 2009
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Review Article|
August 27 2009
Molecular biology, genetics and biochemistry of the repulsive guidance molecule family
Christopher J. Severyn;
Christopher J. Severyn
1Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, U.S.A.
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Ujwal Shinde;
Ujwal Shinde
1Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, U.S.A.
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Peter Rotwein
Peter Rotwein
1
1Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, U.S.A.
1To whom correspondence should be addressed (email rotweinp@ohsu.edu).
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Publisher: Portland Press Ltd
Received:
June 26 2009
Accepted:
July 06 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 422 (3): 393–403.
Article history
Received:
June 26 2009
Accepted:
July 06 2009
Citation
Christopher J. Severyn, Ujwal Shinde, Peter Rotwein; Molecular biology, genetics and biochemistry of the repulsive guidance molecule family. Biochem J 15 September 2009; 422 (3): 393–403. doi: https://doi.org/10.1042/BJ20090978
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