Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10802280 | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | 2013 | 9 Pages |
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.
Keywords
DMEMMAGI-1PTBPC12PDZNGFSHCPAGEERKGSTGFPPBSJnkFBSMBPc-Jun N-terminal kinasemembrane-associated guanylate kinaseDulbecco's modified Eagle's mediumRNA interferenceRNAiMAGUKphosphotyrosine bindingpolyacrylamide gel electrophoresisImmunoprecipitationTrktropomyosin-related kinasefetal bovine serumnerve growth factorPhosphate-buffered salinegreen fluorescent proteinmaltose binding proteinglutathione S-transferase
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Hidenori Ito, Rika Morishita, Ikuko Iwamoto, Makoto Mizuno, Koh-ichi Nagata,