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Role of spastin and protrudin in neurite outgrowth
Author(s) -
Zhang Chuanling,
Li Dan,
Ma Yan,
Yan Jinting,
Yang Baiqing,
Li Peng,
Yu Aiping,
Lu Cailing,
Ma Xu
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24100
Subject(s) - neurite , hereditary spastic paraplegia , zebrafish , microbiology and biotechnology , growth cone , axon , biology , neuroscience , chemistry , gene , genetics , phenotype , in vitro
Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder characterized by retrograde axonal degeneration that primarily affects long spinal neurons. The gene encoding spastin has a well‐established association with HSP, and protrudin is a known binding partner of spastin. Here, we demonstrate that the N ‐terminal domain of protrudin mediates the interaction with spastin, which is responsible for neurite outgrowth. We show that spastin promotes protrudin‐dependent 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‐associated 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 N ‐terminal domain. Moreover, protrudin and spastin may work together to play an indispensable role in motor axon outgrowth. J. Cell. Biochem. 113: 2296–2307, 2012. © 2012 Wiley Periodicals, Inc.