Developmental expression of LC3alpha and beta: absence of fibronectin or autophagy phenotype in LC3beta knockout mice.
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.
Cann
Gordon M
GM
Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA.
Guignabert
Christophe
C
Ying
Lihua
L
Deshpande
Niru
N
Bekker
Janine M
JM
Wang
Lingli
L
Zhou
Bin
B
Rabinovitch
Marlene
M
D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D009420:Nervous System / Q000196:embryology / Q000378:metabolism; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016019:Survival Analysis
D051242:Caveolin 1; D005353:Fibronectins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D020782:Matrix Metalloproteinases