Developmental expression of LC3α and β: Absence of fibronectin or autophagy phenotype in LC3β knockout mice
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.
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LC3A mRNA and protein are not significantly upregulated in the RPE or retina of LC3B-/- mice.
“moreover, there was no significant up-regulation of LC3A mRNA or protein in the RPE or retina (Figures 1A–C), consistent with previous studies using mouse embryonic fibroblasts (Cann et al., 2008).”
From Microtubule-associated protein 1 light chain 3B, (LC3B) is necessary to maintain lipid-mediated homeostasis in the retinal pigment epithelium (2018) · cites this paper as Cann et al., 2008
The LC3B-/- mouse has a null allele due to deletion of exons III and IV of Map1lc3b.
“We examined the role of LC3B in retinal homeostasis using an LC3B-/- mouse, in which deletion of exons III and IV of Map1lc3b results in a null allele (Cann et al., 2008).”
From Microtubule-associated protein 1 light chain 3B, (LC3B) is necessary to maintain lipid-mediated homeostasis in the retinal pigment epithelium (2018) · cites this paper as Cann et al., 2008
LC3B-/- mice develop normally, reach adulthood, and are fertile.
“LC3B-/- mice develop normally, reach adulthood, are fertile”
From Microtubule-associated protein 1 light chain 3B, (LC3B) is necessary to maintain lipid-mediated homeostasis in the retinal pigment epithelium (2018) · cites this paper as Cann et al., 2008
There is no indication of systemic defects in the four previous studies using LC3B-/- mice.
“There is no indication of systemic defects in the 4 previous studies using this mouse (Cann et al., 2008; Chen et al., 2010; Lee et al., 2011; Reed et al., 2015).”
From Microtubule-associated protein 1 light chain 3B, (LC3B) is necessary to maintain lipid-mediated homeostasis in the retinal pigment epithelium (2018) · cites this paper as Cann et al., 2008
Functional redundancy between LC3B and other Atg8 homologs may explain the normal development of LC3B-/- mice.
“This may be due to functional redundancy between LC3B and other Atg8 homologs (e.g., GABARAP) (Cann et al., 2008; Klionsky et al., 2016).”
From Microtubule-associated protein 1 light chain 3B, (LC3B) is necessary to maintain lipid-mediated homeostasis in the retinal pigment epithelium (2018) · cites this paper as Cann et al., 2008
Specifying individual LC3 isoform is necessary because the isoforms have different expression patterns and biology.
“Specifying individual LC3 isoform is necessary as the isoforms have different expression patterns and biology (Cann et al., 2008; Koukourakis et al., 2015).”
From Microtubule-associated protein 1 light chain 3B, (LC3B) is necessary to maintain lipid-mediated homeostasis in the retinal pigment epithelium (2018) · cites this paper as Cann et al., 2008
Mice with global KOs of Atg5 and Atg7 die within a day after birth.
“mice with global KOs of the other autophagy related genes like Atg5 and Atg7 that die within a day after birth (Kuma et al., 2004; Komatsu et al., 2005; Cann et al., 2008).”
From Microtubule-associated protein 1 light chain 3B, (LC3B) is necessary to maintain lipid-mediated homeostasis in the retinal pigment epithelium (2018) · cites this paper as Cann et al., 2008
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References 36 · Cited by 84
- Authors
- Cann, G. M., Guignabert, C., Ying, L., Deshpande, N., Bekker, J. M., Wang, L., Zhou, B., & Rabinovitch, M.
- Affiliations
- Stanford Medicine (US)
- Vanderbilt University (US)
- Corresponding author
- Rabinovitch, Marlene
- Venue
- Developmental Dynamics
- Publisher
- Wiley
- Published
- 2007-12-10
- Volume
- 237
- Issue
- 1
- Pages
- 187-195
- ISSN
- 1058-8388 (ISSN-L)
- 1097-0177
- OpenAlex
- W2092070727
- Cited by
- 84
- References
- 36
- Citations by year
- 2025: 1 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 6 · 2017: 7 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 7 · 2012: 6
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Developmental Dynamics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl074186-17)
- National Heart, Lung, and Blood Institute (R01-HL074186)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- fibronectin, autophagy, embryonic development, knockout mice, embryonic fibroblasts, caveolin-1, LRP1, matrix metalloproteinases, autophagosomes, amino acid starvation, compensatory mechanisms, fetal and neonatal development, brain
- MeSH terms
- Animals, Autophagy, Cells, Cultured, Fibroblasts, Fibronectins, Humans, Mesoderm, Microtubule-Associated Proteins, Nervous System, Phenotype, Blotting, Western, Survival Analysis, In Situ Hybridization, Mice, Knockout, Gene Expression Regulation, Developmental, Protein Isoforms, Matrix Metalloproteinases, Caveolin 1, Mice
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