Dataset Information

?T-catenin: A developmentally dispensable, disease-linked member of the ?-catenin family.

ABSTRACT: ?-Catenins are actin-filament binding proteins and critical subunits of the cadherin-catenin cell-cell adhesive complex. They are found in nominally-defined epithelial (E), neural (N), and testis (T) forms transcribed from three distinct genes. While most of ?-catenin research has focused on the developmentally essential founding member, ?E-catenin, this review discusses recent studies on ?T-catenin (CTNNA3), a developmentally dispensable isoform that is emerging as relevant to cardiac, allergic and neurological diseases.

SUBMITTER: Chiarella SE

PROVIDER: S-EPMC6179130 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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αT-catenin: A developmentally dispensable, disease-linked member of the α-catenin family.

Chiarella Sergio E SE Rabin Erik E EE Ostilla Lorena A LA Flozak Annette S AS Gottardi Cara J CJ

Tissue barriers 20180510 2

α-Catenins are actin-filament binding proteins and critical subunits of the cadherin-catenin cell-cell adhesive complex. They are found in nominally-defined epithelial (E), neural (N), and testis (T) forms transcribed from three distinct genes. While most of α-catenin research has focused on the developmentally essential founding member, αE-catenin, this review discusses recent studies on αT-catenin (CTNNA3), a developmentally dispensable isoform that is emerging as relevant to cardiac, allergic ...[more]

PMID: 29746206

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Project description:BackgroundObesity and its associated morbidities represent the major and most rapidly expanding world-wide health epidemic. Recent genome-wide association studies (GWAS) reveal that single nucleotide polymorphism (SNP) variant in the Family with Sequence Similarity 13, Member A (FAM13A) gene is strongly associated with waist-hip ratio (WHR) with adjustment for body mass index (BMI) (WHRadjBMI). However, the function of FAM13A in adipose development and obesity remains largely uncharacterized.MethodsThe expression of FAM13A in adipose tissue depots were investigated using lean, genetic obese and high fat diet-induced obese (DIO) animal models and during adipocyte differentiation. Stromal vascular cells (SVCs) or 3T3-L1 cells with gain and loss of function of FAM13A were used to determine the involvement of FAM13A in regulating adipocyte differentiation. Adipose development and metabolic homeostasis in Fam13a-/- mice were characterized under normal chow and high fat diet feeding.ResultsMurine FAM13A expression was nutritionally regulated and dramatically reduced in epididymal and subcutaneous fat in genetic and diet-induced obesity. Its expression was enriched in mature adipocytes and significantly upregulated during murine and human adipogenesis potentially through a peroxisome proliferator-activated receptor-gamma (PPARγ)-dependent mechanism. However, Fam13a-/- mice only exhibited a tendency of higher adiposity and were not protected from DIO and insulin resistance. While Fam13a-/- SVCs maintained normal adipogenesis, overexpression of FAM13A in 3T3-L1 preadipocytes downregulated β-catenin signaling and rendered preadipocytes more susceptible to apoptosis. Moreover, FAM13A overexpression largely blocked adipogenesis induced by a standard hormone cocktail, but adipogenesis can be partially rescued by the addition of PPARγ agonist pioglitazone at an early stage of differentiation.ConclusionsOur results suggest that FAM13A is dispensable for adipose development and insulin sensitivity. Yet the expression of FAM13A needs to be tightly controlled in adipose precursor cells for their proper survival and downstream adipogenesis. These data provide novel insights into the link between FAM13A and obesity.

Dataset Information

?T-catenin: A developmentally dispensable, disease-linked member of the ?-catenin family.

Publications

αT-catenin: A developmentally dispensable, disease-linked member of the α-catenin family.

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