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Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry
14:47

Identification of MyoD Interactome Using Tandem Affinity Purification Coupled to Mass Spectrometry

Published on: May 17, 2016

Lepidopteran DALP, and its mammalian ortholog HIC-5, function as negative regulators of muscle differentiation

Y Hu1, P J Cascone, L Cheng

  • 1Molecular and Cellular Biology Program, University of Massachusetts, Amherst, MA 01003, USA.

Proceedings of the National Academy of Sciences of the United States of America
|September 1, 1999
PubMed

Insights

Death-associated LIM-only protein (DALP) and its mammalian ortholog Hic-5 block muscle differentiation and induce apoptosis. These proteins act as conserved switches, regulating myoblast fate and skeletal muscle atrophy.

Area of Science:

  • Muscle development and cell death
  • Molecular biology
  • Insect and mammalian muscle physiology

Background:

  • Myogenesis involves myoblast differentiation into myotubes or apoptosis when trophic support is low.
  • Signal transduction pathways governing myoblast differentiation versus apoptosis remain largely uncharacterized.

Purpose of the Study:

  • To identify and characterize novel signal-transduction molecules involved in myoblast fate determination.
  • To investigate the role of the LIM-only protein DALP and its ortholog Hic-5 in muscle differentiation and apoptosis.

Main Methods:

  • Cloning and characterization of the DALP gene.
  • Forced expression of DALP in Drosophila to study muscle atrophy.
  • Ectopic expression of DALP and Hic-5 in mouse C(2)C(12) myoblasts.
  • Investigating the rescue effects of myoblast contact and MyoD expression.
  • Analyzing Hic-5 expression in dying myoblasts.

Main Results:

  • DALP, a LIM-only zinc-finger protein, is induced during the programmed death of moth intersegmental muscles.
  • Forced expression of DALP in Drosophila causes skeletal muscle atrophy.
  • Ectopic DALP or Hic-5 expression inhibits differentiation and induces apoptosis in mouse myoblasts.
  • These inhibitory effects are reversible by myoblast contact or MyoD expression.
  • Hic-5 is significantly upregulated in myoblasts undergoing apoptosis due to trophic factor withdrawal.

Conclusions:

  • DALP and Hic-5 function as phylogenetically conserved regulators of myoblast fate.
  • These proteins act upstream of MyoD, serving as molecular switches to either block muscle differentiation or induce apoptosis.
  • DALP and Hic-5 are key players in the programmed cell death of muscle cells.

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