Caveolin-3 promotes glycometabolism, growth and proliferation in muscle cells.

Lina Shang,Yiyuan Huang,Lihui Yang,Jing Xian,Tingting Chen,Yuanheng Huang,Qin Huang,Wensheng Lu,Yufeng Deng

doi:10.1371/journal.pone.0189004

Abstract

ObjectiveCaveolin-3 (CAV3) protein is known to be expressed specifically in various myocytes, but its physiological function remains unclear. CAV3, located at the cell membrane, may promote the sensitivity of the Akt signaling pathway, which is closely related to glucose metabolism and to cell growth and proliferation.MethodsThe CAV3 gene was stably transfected into C2C12 muscle cells, and the effects were evaluated by biochemical assays, WB and confocal microscopy for the observation of cellular glucose metabolism, growth and proliferation, and the effect of CAV3 on the Akt signaling pathway with no insulin stimulation.ResultsAfter C2C12 cells were transfected with the mouse CAV3 gene, which increased CAV3 expression, the abundance of the CAV3 and GLUT4 proteins on the cell membrane increased, but the total GLUT4 protein content of the cell was unchanged. Glucose uptake was increased, and this did not affect the glycogen synthesis, but the cell surface area and cell proliferation increased. While there were significant increases in p-Akt and p-p70s6K, which is a downstream component of Akt signaling, the level of GSK3β protein, another component of Akt signaling did not change.ConclusionsThe muscle, CAV3 protein can activate Akt signaling, increase GLUT4 protein localization in the cell membrane, increase glucose uptake, and promote myocyte growth and proliferation. CAV3 protein has a physiological role in glycometabolism, growth and proliferation, independent of insulin stimulation.

Highlights

Caveolin (CAV) is a Caveolae-associated protein in cell membranes
After C2C12 cells were transfected with the mouse CAV3 gene, which increased CAV3 expression, the abundance of the CAV3 and GLUT4 proteins on the cell membrane increased, but the total GLUT4 protein content of the cell was unchanged
CAV3 protein has a physiological role in glycometabolism, growth and proliferation, independent of insulin stimulation

Summary

Introduction

Caveolin (CAV) is a Caveolae-associated protein in cell membranes. The Caveolin gene family has three subtypes: CAV1, CAV2 and CAV3. CAV3 protein was first cloned and identified in 1996 and is expressed in muscle cells, including skeletal muscle, cardiac muscle and smooth muscle cells, and is known as M-caveolin. The Caveolin-3 gene is located on human chromosome 3 and produces a protein consisting of 151 amino acids. It consists of an N-terminal region, transmembrane region and C-terminal region. Its N-terminal scaffolding domain (CSD) regulates a variety of signaling molecules including eNOS, Gprotein, adrenergic receptor, protein kinase C monomers, and Src family protein kinases, and it has substantial effects on numerous aspects of muscle physiology, including muscular dystrophin, cholesterol transport, intracellular signaling, tumor suppression, and myocyte synthesis [1], but its physiological function in skeletal muscle is not yet fully understood

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