Peptides derived from repulsive guidance molecule act as antagonists.
Repulsive guidance molecule (RGM) is a membrane-bound protein that was originally identified as an axon guidance molecule in the visual system [T. Yamashita, B.K. Mueller, K. Hata, Neogenin and RGM signaling in the central nervous system, Curr. Opin. Neurobiol. 17 (2007) 29-34]. Functional studies in Xenopus and chick embryos have revealed the roles of RGM in axon guidance and laminar patterning, while those in mouse embryos have demonstrated its function in regulating the cephalic neural tube closure. Importantly, RGM inhibition enhanced the growth of injured axons and promoted functional recovery after spinal cord injury in rats. Here, we identified two RGMa-derived peptides that functioned as antagonists against RGMa. The peptides studied in vitro dose-dependently suppressed the neurite growth inhibition and growth cone collapse induced by RGMa. Thus, these peptides are promising reagents to treat injuries of the central nervous system.
Suda
Masayoshi
M
Department of Neurobiology, Graduate School of Medicine, Chiba University, Japan.
Hata
Katsuhiko
K
Sawada
Aika
A
Nakamura
Yuka
Y
Kubo
Takekazu
T
Yamaguchi
Atsushi
A
Yamashita
Toshihide
T
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D058851:GPI-Linked Proteins; D020439:Growth Cones / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D016501:Neurites / Q000187:drug effects; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010455:Peptides; C502259:RGM protein, rat