title: Inhibition of Nischarin Expression Promotes Neurite Outgrowth through Regulation of PAK Activity.
abstract: Nischarin is a cytoplasmic protein expressed in various organs that plays an inhibitory role in cell migration and invasion and the carcinogenesis of breast cancer cells. We previously reported that Nischarin is highly expressed in neuronal cell lines and is differentially expressed in the brain tissue of adult rats. However, the physiological function of Nischarin in neural cells remains unknown. Here, we show that Nischarin is expressed in rat primary cortical neurons but not in astrocytes. Nischarin is localized around the nucleus and dendrites. Using shRNA to knockdown the expression of endogenous Nischarin significantly increases the percentage of neurite-bearing cells, remarkably increases neurite length, and accelerates neurite extension in neuronal cells. Silencing Nischarin expression also promotes dendrite elongation in rat cortical neurons where Nischarin interacts with p21-activated kinase 1/2 (PAK1/2) and negatively regulates phosphorylation of both PAK1 and PAK2. The stimulation of neurite growth observed in cells with decreased levels of Nischarin is partially abolished by IPA3-mediated inhibition of PAK1 activity. Our findings indicate that endogenous Nischarin inhibits neurite outgrowth by blocking PAK1 activation in neurons.
authors.affiliation: Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou, 310015, China.
authors.forename: Yuemin
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Physiology, School of Medicine, Quzhou College of Technology, Quzhou, 324000, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou, 310015, China.
authors.forename: Lingchao
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Pathology, Jiaxing Second Hospital, Jiaxing, 314000, China.
authors.forename: Ruyi
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou, 310015, China.
authors.forename: Linghui
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D054755:Imidazoline Receptors; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D016501:Neurites / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D054462:p21-Activated Kinases / Q000378:metabolism*
chemical_list: D054755:Imidazoline Receptors; D047908:Intracellular Signaling Peptides and Proteins; C503041:Nisch protein, mouse; C519767:Nisch protein, rat; D054462:p21-Activated Kinases