title: RGMs: Structural Insights, Molecular Regulation, and Downstream Signaling.
abstract: Although originally discovered as neuronal growth cone-collapsing factors, repulsive guidance molecules (RGMs) are now known as key players in many fundamental processes, such as cell migration, differentiation, iron homeostasis, and apoptosis, during the development and homeostasis of many tissues and organs, including the nervous, skeletal, and immune systems. Furthermore, three RGMs (RGMa, RGMb/DRAGON, and RGMc/hemojuvelin) have been linked to the pathogenesis of various disorders ranging from multiple sclerosis (MS) to cancer and juvenile hemochromatosis (JHH). While the molecular details of these (patho)biological effects and signaling modes have long remained unknown, recent studies unveil several exciting and novel aspects of RGM processing, ligand-receptor interactions, and downstream signaling. In this review, we highlight recent advances in the mechanisms-of-action and function of RGM proteins.
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Siebold
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Krembil Research Institute, 60 Leonard Street, M5T 2S8, Toronto, ONT, Canada.
authors.forename: Philippe P
authors.initials: PP
authors.lastname: Monnier
authors.affiliation: Neuroscience Discovery Research, Abbvie, Knollstrasse 50, 67061 Ludwigshafen, Germany.
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Mueller
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center, Universiteitsweg 100, 3584 CG, Utrecht, The Netherlands. Electronic address: r.j.pasterkamp@umcutrecht.nl.
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Pasterkamp
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008024:Ligands; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface
keywords: BMP; axon guidance; immune system; iron metabolism; neogenin; proteolytic cleavage