Developmental expression of LC3alpha and beta: absence of fibronectin or autophagy phenotype in LC3beta knockout mice

Dev Dyn. 2008 Jan;237(1):187-95. doi: 10.1002/dvdy.21392.

Abstract

Murine light chain 3 (LC3) exists as two isoforms, LC3alpha and beta: LC3beta is an RNA-binding protein that enhances fibronectin (FN) mRNA translation, and is also a marker of autophagy. We report embryonic expression patterns for LC3alpha and LC3beta, with some overlap but notable differences in the brain, and in tissues of non-neuronal origin. LC3beta knockout (-/-) mice develop normally without a compensatory increase in LC3alpha. LC3beta-/- embryonic fibroblasts (MEFs) exhibit reduced FN synthesis but maintain wild type (WT) levels of FN protein. No significant changes in proteins associated with FN turnover, i.e., caveolin-1, LRP-1, or matrix metalloproteinases were identified. Autophagosomes form in amino acid-starved LC3beta-/-MEFs, and Caesarean-delivered pups survive as long as WT pups without an increase in LC3-related proteins linked to autophagy. These results suggest novel compensatory mechanisms for loss of LC3beta, ensuring proper FN accumulation and autophagy during fetal and neonatal life.

Publication types

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

MeSH terms

  • Animals
  • Autophagy / genetics
  • Autophagy / physiology
  • Blotting, Western
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibronectins / genetics
  • Fibronectins / metabolism*
  • Gene Expression Regulation, Developmental*
  • Humans
  • In Situ Hybridization
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / physiology
  • Nervous System / embryology
  • Nervous System / metabolism
  • Phenotype
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Isoforms / physiology
  • Survival Analysis

Substances

  • Caveolin 1
  • Fibronectins
  • Map1lc3b protein, mouse
  • Microtubule-Associated Proteins
  • Protein Isoforms
  • Matrix Metalloproteinases