Molecular and cellular mechanisms of spastin in neural development and disease (Review)

Spastin is a microtubule (MT)-severing enzyme identified from mutations of hereditary spastic paraplegia in 1999 and extensive studies indicate its vital role in various cellular activities. In the past two decades, efforts have been made to understand the underlying molecular mechanisms of how spastin is linked to neural development and disease. Recent studies on spastin have unraveled the mechanistic processes of its MT-severing activity and revealed that spastin acts as an MT amplifier to mediate its remodeling, thus providing valuable insight into the molecular roles of spastin under physiological conditions. In addition, recent research has revealed multiple novel molecular mechanisms of spastin in cellular biological pathways, including endoplasmic reticulum shaping, calcium trafficking, fatty acid trafficking, as well as endosomal fission and trafficking. These processes are closely involved in axonal and dendritic development and maintenance. The current review presents recent biological advances regarding the molecular mechanisms of spastin at the cellular level and provides insight into how it affects neural development and disease.