Two novel members of the ABLIM protein family, ABLIM-2 and -3, associate with STARS and directly bind F-actin

J Biol Chem. 2007 Mar 16;282(11):8393-403. doi: 10.1074/jbc.M607549200. Epub 2006 Dec 28.

Abstract

In addition to regulating cell motility, contractility, and cytokinesis, the actin cytoskeleton plays a critical role in the regulation of transcription and gene expression. We have previously identified a novel muscle-specific actin-binding protein, STARS (striated muscle activator of Rho signaling), which directly binds actin and stimulates serum-response factor (SRF)-dependent transcription. To further dissect the STARS/SRF pathway, we performed a yeast two-hybrid screen of a skeletal muscle cDNA library using STARS as bait, and we identified two novel members of the ABLIM protein family, ABLIM-2 and -3, as STARS-interacting proteins. ABLIM-1, which is expressed in retina, brain, and muscle tissue, has been postulated to function as a tumor suppressor. ABLIM-2 and -3 display distinct tissue-specific expression patterns with the highest expression levels in muscle and neuronal tissue. Moreover, these novel ABLIM proteins strongly bind F-actin, are localized to actin stress fibers, and synergistically enhance STARS-dependent activation of SRF. Conversely, knockdown of endogenous ABLIM expression utilizing small interfering RNA significantly blunted SRF-dependent transcription in C2C12 skeletal muscle cells. These findings suggest that the members of the novel ABLIM protein family may serve as a scaffold for signaling modules of the actin cytoskeleton and thereby modulate transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Humans
  • LIM Domain Proteins
  • Mice
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism*
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism
  • Protein Binding
  • Retina / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Two-Hybrid System Techniques

Substances

  • Ablim2 protein, mouse
  • Ablim3 protein, mouse
  • Abra protein, mouse
  • Actins
  • LIM Domain Proteins
  • Microfilament Proteins

Associated data

  • GENBANK/DQ413174
  • GENBANK/DQ413175
  • GENBANK/DQ413176
  • GENBANK/DQ413177