Elavl3 is essential for the maintenance of Purkinje neuron axons

Sci Rep. 2018 Feb 9;8(1):2722. doi: 10.1038/s41598-018-21130-5.

Abstract

Neuronal Elav-like (nElavl or neuronal Hu) proteins are RNA-binding proteins that regulate RNA stability and alternative splicing, which are associated with axonal and synaptic structures. nElavl proteins promote the differentiation and maturation of neurons via their regulation of RNA. The functions of nElavl in mature neurons are not fully understood, although Elavl3 is highly expressed in the adult brain. Furthermore, possible associations between nElavl genes and several neurodegenerative diseases have been reported. We investigated the relationship between nElavl functions and neuronal degeneration using Elavl3-/- mice. Elavl3-/- mice exhibited slowly progressive motor deficits leading to severe cerebellar ataxia, and axons of Elavl3-/- Purkinje cells were swollen (spheroid formation), followed by the disruption of synaptic formation of axonal terminals. Deficit in axonal transport and abnormalities in neuronal polarity was observed in Elavl3-/- Purkinje cells. These results suggest that nElavl proteins are crucial for the maintenance of axonal homeostasis in mature neurons. Moreover, Elavl3-/- mice are unique animal models that constantly develop slowly progressive axonal degeneration. Therefore, studies of Elavl3-/- mice will provide new insight regarding axonal degenerative processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axonal Transport
  • Axons / metabolism
  • Axons / pathology*
  • Cells, Cultured
  • Cerebellar Ataxia / etiology*
  • Cerebellar Ataxia / metabolism
  • Cerebellar Ataxia / pathology
  • ELAV-Like Protein 3 / physiology*
  • Gene Expression Regulation
  • Kinesin / genetics
  • Kinesin / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Knockout
  • Motor Disorders / etiology*
  • Motor Disorders / metabolism
  • Motor Disorders / pathology
  • Nerve Degeneration / etiology*
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Neurons / metabolism
  • Neurons / pathology*
  • Purkinje Cells / metabolism
  • Purkinje Cells / pathology*

Substances

  • ELAV-Like Protein 3
  • Elavl3 protein, mouse
  • Kif3a protein, mouse
  • Kif3c protein, mouse
  • Kinesin