Promotion of neurite and filopodium formation by CD47: roles of integrins, Rac, and Cdc42.
Axon extension during development is guided by many factors, but the signaling mechanisms responsible for its regulation remain largely unknown. We have now investigated the role of the transmembrane protein CD47 in this process in N1E-115 neuroblastoma cells. Forced expression of CD47 induced the formation of neurites and filopodia. Furthermore, an Fc fusion protein containing the extracellular region of the CD47 ligand SHPS-1 induced filopodium formation, and this effect was enhanced by CD47 overexpression. SHPS-1-Fc also promoted neurite and filopodium formation triggered by serum deprivation. Inhibition of Rac or Cdc42 preferentially blocked CD47-induced formation of neurites and filopodia, respectively. Overexpression of CD47 resulted in the activation of both Rac and Cdc42. The extracellular region of CD47 was sufficient for the induction of neurite formation by forced expression, but the entire structure of CD47 was required for enhancement of filopodium formation by SHPS-1-Fc. Neurite formation induced by CD47 was also inhibited by a mAb to the integrin beta3 subunit. These results indicate that the interaction of SHPS-1 with CD47 promotes neurite and filopodium formation through the activation of Rac and Cdc42, and that integrins containing the beta3 subunit participate in the effect of CD47 on neurite formation.
Miyashita
Motoaki
M
Biosignal Research Center, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
Ohnishi
Hiroshi
H
Okazawa
Hideki
H
Tomonaga
Hiroyasu
H
Hayashi
Akiko
A
Fujimoto
Tetsuro-Takahiro
TT
Furuya
Nobuhiko
N
Matozaki
Takashi
T
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000943:Antigens, Differentiation / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D051928:CD47 Antigen; D002478:Cells, Cultured; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000494:pharmacology; D039661:Integrin beta3 / Q000276:immunology / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D009154:Mutation / Q000235:genetics; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D016501:Neurites / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011554:Pseudopodia / Q000648:ultrastructure*; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology; D000077191:Wortmannin; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000502:physiology; D020741:rho GTP-Binding Proteins / Q000502:physiology*
D000730:Androstadienes; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D051928:CD47 Antigen; C497895:Cd47 protein, mouse; D007141:Immunoglobulin Fc Fragments; D039661:Integrin beta3; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D010455:Peptides; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic; C057986:echistatin; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins; D000077191:Wortmannin