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Here, we demonstrate that the<jats:italic>N<\/jats:italic>\u2010terminal domain of protrudin mediates the interaction with spastin, which is responsible for neurite outgrowth. We show that spastin promotes protrudin\u2010dependent neurite outgrowth in PC12 cells. To further confirm these physiological functions in vivo, we microinjected zebrafish embryos with various protrudin\/spastin mRNA and morpholinos. The results suggest that the spinal cord motor neuron axon outgrowth of zebrafish is regulated by the interaction between spastin and protrudin. In addition, the putative HSP\u2010associated protrudinG191V mutation was shown to alter the subcellular distribution and impair the yolk sac extension of zebrafish, but without significant defects in neurite outgrowth both in PC12 cells and zebrafish. Taken together, our findings indicate that protrudin interacts with spastin and induces axon formation through its<jats:italic>N<\/jats:italic>\u2010terminal domain. Moreover, protrudin and spastin may work together to play an indispensable role in motor axon outgrowth. J. Cell. Biochem. 113: 2296\u20132307, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcb.24100","type":"journal-article","created":{"date-parts":[[2012,2,14]],"date-time":"2012-02-14T14:55:03Z","timestamp":1329231303000},"page":"2296-2307","source":"Crossref","is-referenced-by-count":28,"title":["Role of spastin and protrudin in neurite 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