title: MAGI-1 acts as a scaffolding molecule for NGF receptor-mediated signaling pathway.
abstract: We have recently found that the membrane-associated guanylate kinase with inverted organization-1 (MAGI-1) was enriched in rat nervous tissues such as the glomeruli in olfactory bulb of adult rats and dorsal root entry zone in spinal cord of embryonic rats. In addition, we revealed the localization of MAGI-1 in the growth cone of the primary cultured rat dorsal root ganglion cells. These results point out the possibility that MAGI-1 is involved in the regulation of neurite extension or guidance. In this study, we attempted to reveal the physiological role(s) of MAGI-1 in neurite extension. We found that RNA interference (RNAi)-mediated knockdown of MAGI-1 caused inhibition of nerve growth factor (NGF)-induced neurite outgrowth in PC12 rat pheochromocytoma cells. To clarify the involvement of MAGI-1 in NGF-mediated signal pathway, we tried to identify binding partners for MAGI-1 and identified p75 neurotrophin receptor (p75NTR), a low affinity NGF receptor, and Shc, a phosphotyrosine-binding adaptor. These three proteins formed an immunocomplex in PC12 cells. Knockdown as well as overexpression of MAGI-1 caused suppression of NGF-stimulated activation of the Shc-ERK pathway, which is supposed to play important roles in neurite outgrowth of PC12 cells. These results indicate that MAGI-1 may act as a scaffolding molecule for NGF receptor-mediated signaling pathway.
authors.affiliation: Department of Molecular Neurobiology, Aichi Human Service Center, Kasugai, Aichi, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ito
authors.forename: Rika
authors.initials: R
authors.lastname: Morishita
authors.forename: Ikuko
authors.initials: I
authors.lastname: Iwamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Mizuno
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D051528:Guanylate Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D016501:Neurites / Q000378:metabolism*; D055495:Neurogenesis; D016716:PC12 Cells; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020800:Receptor, Nerve Growth Factor; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; C068313:Ngfr protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; D051528:Guanylate Kinases; C508141:Magi1 protein, rat
keywords: DMEM; Dulbecco's modified Eagle's medium; ERK; FBS; GFP; GST; IP; JNK; MAGI-1; MAGUK; MBP; NGF; PAGE; PBS; PC12; PDZ; PSD-95/Discs Large/Zona Occludens; PTB; RNA interference; RNAi; Shc; Trk; c-Jun N-terminal kinase; fetal bovine serum; glutathione S-transferase; green fluorescent protein; immunoprecipitation; maltose binding protein; membrane-associated guanylate kinase; membrane-associated guanylate kinase with inverted organization-1; nerve growth factor; phosphate-buffered saline; phosphotyrosine binding; polyacrylamide gel electrophoresis; tropomyosin-related kinase