Human synapsin I mediates the function of nuclear respiratory factor 1 in neurite outgrowth in neuroblastoma IMR-32 cells

✍ Scribed by Jen-Ling Wang; Wen-Teng Chang; Chih-Wei Tong; Kimitoshi Kohno; A-Min Huang

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 412 KB
• Volume: 87
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.22059

✦ Synopsis

Abstract

Nuclear respiratory factor (NRF)‐1 is a transcription factor with a novel function in neurite outgrowth. Synapsin I protein is a well‐known phosphoprotein in neuronal terminals and has been implicated in neuronal differentiation. Human synapsin I gene promoter has a putative NRF‐1 responsive element (NRE), but it is not known whether this NRE is functional. We hypothesized that synapsin I is downstream of NRF‐1 and mediates its function in neurite outgrowth. Gel electrophoretic mobility shift assays, chromatin immunoprecipitation, site‐directed mutagenesis, and promoter studies indicated that NRF‐1 is a positive regulator of synapsin I promoter. Exogenous NRF‐1 overexpression increased synapsin I protein levels in IMR‐32 and HEK293T cells. Serum deprivation, which induces neurite outgrowth in IMR‐32 cells, increased the binding activity of NRF‐1 to synapsin I NRE and induced alternating synapsin I protein expression. Down‐regulating synapsin I expression markedly decreased the percentage of neurite‐bearing cells and the length of the longest neurite in IMR‐32 cells that stably or transiently overexpressed NRF‐1. We conclude that the human synapsin I gene is positively regulated by NRF‐1 and mediates the function of NRF‐1 in neurite outgrowth. © 2009 Wiley‐Liss, Inc.