title: Role of spastin and protrudin in neurite outgrowth.
abstract: 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.
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Chuanling
authors.initials: C
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Jinting
authors.initials: J
authors.lastname: Yan
authors.forename: Baiqing
authors.initials: B
authors.lastname: Yang
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Aiping
authors.initials: A
authors.lastname: Yu
authors.forename: Cailing
authors.initials: C
authors.lastname: Lu
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D060172:Morpholinos / Q000008:administration & dosage; D009046:Motor Neurons / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells; D034622:RNA Interference; D012333:RNA, Messenger / Q000008:administration & dosage; D034741:RNA, Small Interfering; D051381:Rats; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000074181:Spastin; D013116:Spinal Cord / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology
chemical_list: D060172:Morpholinos; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; C513390:ZFYVE27 protein, human; D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human