Role of Spastin and Protrudin in Neurite Outgrowth

被引:24
作者
Zhang, Chuanling [1 ]
Li, Dan [1 ]
Ma, Yan [1 ]
Yan, Jinting [1 ]
Yang, Baiqing [1 ]
Li, Peng [1 ]
Yu, Aiping [2 ]
Lu, Cailing [1 ]
Ma, Xu [1 ]
机构
[1] Natl Res Inst Family Planning, Dept Genet, Beijing 100081, Peoples R China
[2] Beijing Inst Radiat Med, Dept Expt Hematol, Beijing, Peoples R China
关键词
PROTRUDIN; SPASTIN; PROTEIN INTERACTION; NEURITE OUTGROWTH; PARAPLEGIA PROTEIN; AXON OUTGROWTH; TRANSPORT; MICROTUBULES; EXTENSION; DYNAMICS; SPG3A; GENE;
D O I
10.1002/jcb.24100
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 sub cellular 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. (C) 2012 Wiley Periodicals, Inc.
引用
收藏
页码:2296 / 2307
页数:12
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