MKLs: Co-Factors of Serum Response Factor (SRF) in Neuronal Responses

Int J Biochem Cell Biol. 2012 Sep;44(9):1444-7. doi: 10.1016/j.biocel.2012.05.008. Epub 2012 May 22.

Abstract

Serum response factor (SRF) is a major transcription factor that regulates activity-driven gene expression in neurons. Activation of SRF-driven transcription occurs through its interaction with two families of co-factors: ternary complex factor (TCF) and myocardin-related transcription factors (MRTFs). This review focuses on the MRTF family members MKL1 (MAL/MRTF-A/BSAC) and MKL2 (MRTF-B/MAL16). MKLs share several high-homology domains but a low level of sequence identity in the transactivation domain. Both co-activators are expressed in the brain and regulate SRF-dependent gene expression. MKL1 and MKL2 function as major co-activators of SRF function in the developing mouse brain. MKLs inactivation causes ineffective neuronal migration and aberrant neurite outgrowth during development. Moreover, inhibition of MKL1 or MKL2 by short-hairpin RNAs results in a decreased number of dendritic processes and dendritic length. Altogether, MKLs appear to regulate plasticity-related structural changes in neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Diseases / metabolism
  • Brain Diseases / pathology
  • Gene Expression Regulation
  • Humans
  • Neurons / metabolism*
  • Neurons / pathology
  • Serum Response Factor / metabolism*
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*

Substances

  • Serum Response Factor
  • Transcription Factors