PUBLICATION

Role of spastin and protrudin in neurite outgrowth

Authors
Zhang, C., Li, D., Ma, Y., Yan, J., Yang, B., Li, P., Yu, A., Lu, C., and Ma, X.
ID
ZDB-PUB-120514-4
Date
2012
Source
Journal of cellular biochemistry   113(7): 2296-2307 (Journal)
Registered Authors
Keywords
protrudin, spastin, protein interaction, neurite outgrowth
MeSH Terms
  • Adenosine Triphosphatases/genetics
  • Adenosine Triphosphatases/metabolism*
  • Animals
  • Cell Line
  • HEK293 Cells
  • Humans
  • Morpholinos/administration & dosage
  • Motor Neurons/metabolism*
  • Neurites/physiology*
  • PC12 Cells
  • RNA Interference
  • RNA, Messenger/administration & dosage
  • RNA, Small Interfering
  • Rats
  • Spastic Paraplegia, Hereditary/genetics
  • Spastic Paraplegia, Hereditary/metabolism*
  • Spastic Paraplegia, Hereditary/pathology
  • Spinal Cord/metabolism
  • Vesicular Transport Proteins/genetics
  • Vesicular Transport Proteins/metabolism*
  • Zebrafish/embryology
PubMed
22573551 Full text @ J. Cell. Biochem.
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.

Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping