REST levels affect the functional expression of voltage dependent calcium channels and the migratory activity in immortalized GnRH neurons

Neurosci Lett. 2016 Aug 26:629:19-25. doi: 10.1016/j.neulet.2016.06.050. Epub 2016 Jun 24.

Abstract

The repressor element-1 silencing transcription factor (REST) has emerged as a key controller of neuronal differentiation and has been shown to play a critical role in the expression of the neuronal phenotype; however, much has still to be learned about its role at specific developmental stages and about the functional targets affected. Among these targets, calcium signaling mechanisms are critically dependent on the developmental stage and their full expression is a hallmark of the mature, functional neuron. We have analyzed the role played by REST in GN11 cells, an immortalized cell line derived from gonadotropin hormone releasing hormone (GnRH) neurons at an early developmental stage, electrically non-excitable and with a strong migratory activity. We show for the first time that functional voltage-dependent calcium channels are expressed in wild type GN11 cells; down-regulation of REST by a silencing approach shifts these cells towards a more differentiated phenotype, increasing the functional expression of P/Q-type channels and reducing their migratory potential.

Keywords: Calcium channels; GN11 cells; GT1-7 cells; GnRH neurons; Neuronal migration; REST/NRSF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels, P-Type / metabolism*
  • Calcium Channels, Q-Type / metabolism*
  • Calcium Signaling
  • Cell Culture Techniques
  • Cell Movement*
  • Cell Proliferation
  • Gene Knockdown Techniques
  • Gonadotropin-Releasing Hormone / metabolism*
  • Mice
  • Neurons / metabolism*
  • Neurons / physiology*
  • Repressor Proteins / metabolism*

Substances

  • Calcium Channels, P-Type
  • Calcium Channels, Q-Type
  • RE1-silencing transcription factor
  • Repressor Proteins
  • Gonadotropin-Releasing Hormone