Inhibition of branching and spine maturation by repulsive guidance molecule in cultured cortical neurons.
Repulsive guidance molecule (RGM) is a membrane-bound protein that was originally identified as an axon guidance molecule in the visual system. Functional studies in Xenopus and chick embryos revealed the roles of RGM in axon guidance and laminar patterning, while those in mouse embryos demonstrated its function in regulating cephalic neural tube closure. Moreover, RGM inhibition enhanced the growth of injured axons and promoted functional recovery after spinal cord injury in rats. Here, we demonstrate in vitro that RGMa, an RGM homolog, inhibits neurite growth and cortical neuron branching on mouse embryonic day 16. Further, exposure of cultured neurons to RGMa significantly reduced the number of colocalized immunoreactive clusters of synapsin 1 and PSD-95 in the spines. This RGMa-mediated inhibition of the assembly of presynaptic and postsynaptic components suggests a role of RGMa in inhibiting mature synapse formation. Thus, RGMa may negatively regulate neuronal network formation in cortical neurons.
Department of Neurobiology, Graduate School of Medicine, Chiba University, Japan.
Junko
J
Yoshida
Takekazu
T
Kubo
Toshihide
T
Yamashita
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D000076122:Disks Large Homolog 4 Protein; D058851:GPI-Linked Proteins; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000494:pharmacology / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011712:Pyramidal Tracts / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D016704:Synapsins / Q000378:metabolism
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C483496:Rgma protein, mouse; D016704:Synapsins; D051528:Guanylate Kinases