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T-cadherin, a major adiponectin binding partner, suppresses ERK signaling in metabolic tissues

ABSTRACT: T-cadherin, which is a major adiponectin binding partner, exerts various organ-protective effects. However, the specific changes in intracellular signaling that are induced by T-cadherin in metabolic tissues/cells remain unclear. We demonstrated that T-cadherin suppresses ERK signaling in both cultured cells and murine tissues. T-cadherin knockdown increased ERK phosphorylation in C2C12 myocytes and F2 endothelial cells, whereas T-cadherin overexpression suppressed ERK phosphorylation. Proteomic analysis revealed that many proteins that are downstream targets of ERK signaling were upregulated by T-cadherin knockdown in myocytes. T-cadherin knockdown in myocytes or knockout in heart or skeletal muscles altered the levels of membrane proteins that are involved in signal transduction, including IGF1R and EGFR. Ablation of T-cadherin in mice was accompanied by increased ERK signaling, leading to increased cardiac hypertrophy and decreased appropriate muscle atrophy during starvation. Thus, T-cadherin, whose protein expression is maintained by adiponectin, modulates intracellular signaling and regulates cardiac and skeletal muscle homeostasis. C2C12 myotubes were transfected with control or T-cadherin siRNA and treated with or without adiponectin (APN) (10 μg/mL) for 24 h (n=4 per group).

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Hirofumi Nagao, Iichiro Shimomura

PROVIDER: PXD066195 | JPOST Repository | Thu Feb 19 00:00:00 GMT 2026

REPOSITORIES: jPOST

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			Action	DRS
	24PS0021_Sample01.raw	Raw
	24PS0021_Sample02.raw	Raw
	24PS0021_Sample03.raw	Raw
	24PS0021_Sample04.raw	Raw
	24PS0021_Sample05.raw	Raw

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