Neuronal roles of the integrin-associated protein (IAP/CD47) in developing cortical neurons.
Little is known about the role of the integrin-associated protein (IAP, or CD47) in neuronal development and its function in the central nervous system. We investigated neuronal responses in IAP-overexpressing cortical neurons using a virus-gene transfer system. We found that dendritic outgrowth was significantly enhanced in IAP (form 4)-transfected neurons. Furthermore, synaptic proteins including synaptotagmin, syntaxin, synapsin I, and SNAP25 (25-kDa synaptosomal associated protein) were up-regulated. In accordance with this finding, the release of the excitatory transmitter glutamate and the frequencies of Ca2+ oscillations (glutamate-mediated synaptic transmission) were increased. Interestingly, the overexpression of IAP activated mitogen-activated protein kinase (MAPK), and this activation was required for the IAP-dependent biological effects. After down-regulation of the endogenous IAP by small interfering RNA, MAPK activity, synaptic protein levels, and glutamate release decreased. These observations suggest that the IAP plays important roles in dendritic outgrowth and synaptic transmission in developing cortical neurons through the activation of MAPK.
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry of Japan, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. numakawa@ncnp.go.jp
Tadahiro
T
Numakawa
Tetsuya
T
Ishimoto
Shingo
S
Suzuki
Yumiko
Y
Numakawa
Naoki
N
Adachi
Tomoya
T
Matsumoto
Daisaku
D
Yokomaku
Hisatsugu
H
Koshimizu
Kazuhiro E
KE
Fujimori
Ryota
R
Hashimoto
Takahisa
T
Taguchi
Hiroshi
H
Kunugi
D000256:Adenoviridae / Q000235:genetics; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology*; D051928:CD47 Antigen; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D015536:Down-Regulation; D018014:Gene Transfer Techniques; D018698:Glutamic Acid / Q000737:chemistry; D007150:Immunohistochemistry; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000737:chemistry; D009474:Neurons / Q000378:metabolism*; D009991:Oscillometry; D050765:Qa-SNARE Proteins; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D009435:Synaptic Transmission; D050825:Synaptosomal-Associated Protein 25; D013574:Synaptosomes / Q000378:metabolism; D050857:Synaptotagmins; D015854:Up-Regulation; D014780:Viruses / Q000235:genetics
D000596:Amino Acids; D015703:Antigens, CD; D051928:CD47 Antigen; D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D034741:RNA, Small Interfering; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D050857:Synaptotagmins; D018698:Glutamic Acid; D002118:Calcium