Developmental expression of LC3α and β: Absence of fibronectin or autophagy phenotype in LC3β knockout mice

Murine light chain 3 (LC3) exists as two isoforms, LC3α and β: LC3β is an RNA-binding protein that enhances fibronectin (FN) mRNA translation, and is also a marker of autophagy. We report embryonic expression patterns for LC3α and LC3β, with some overlap but notable differences in the brain, and in tissues of non-neuronal origin. LC3β knockout (-/-) mice develop normally without a compensatory increase in LC3α. LC3β-/- 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 LC3β-/-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 LC3β, ensuring proper FN accumulation and autophagy during fetal and neonatal life.