MYH10 Governs Adipocyte Function and Adipogenesis through Its Interaction with GLUT4.

Nadav Kislev,Michael Egozi,Dafna Benayahu,Lisa Mor-Yossef Moldovan,Rakefet Barak

doi:10.3390/ijms23042367

Nadav Kislev, Michael Egozi + Show 3 more

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https://doi.org/10.3390/ijms23042367

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Abstract

Adipogenesis is dependent on cytoskeletal remodeling that determines and maintains cellular shape and function. Cytoskeletal proteins contribute to the filament-based network responsible for controlling the shape of adipocytes and promoting the intracellular trafficking of cellular components. Currently, the understanding of these mechanisms and their effect on differentiation and adipocyte function remains incomplete. In this study, we identified the non-muscle myosin 10 (MYH10) as a novel regulator of adipogenesis and adipocyte function through its interaction with the insulin-dependent glucose transporter 4 (GLUT4). MYH10 depletion in preadipocytes resulted in impaired adipogenesis, with knockdown cells exhibiting an absence of morphological alteration and molecular signals. MYH10 was shown in a complex with GLUT4 in adipocytes, an interaction regulated by insulin induction. The missing adipogenic capacity of MYH10 knockdown cells was restored when the cells took up GLUT4 vesicles from neighbor wildtype cells in a co-culture system. This signaling cascade is regulated by the protein kinase C ζ (PKCζ), which interacts with MYH10 to modify the localization and interaction of both GLUT4 and MYH10 in adipocytes. Overall, our study establishes MYH10 as an essential regulator of GLUT4 translocation, affecting both adipogenesis and adipocyte function, highlighting its importance in future cytoskeleton-based studies in adipocytes.

Highlights

The process of adipocyte differentiation is termed adipogenesis
Cytoskeletal proteins are involved in the terminal differentiation phase and the insulin signaling pathway, where they are needed as a filament-based network for translocation of glucose transporter 4 (GLUT4) and other related processes [10,11,12,13,14,15]
As part of the analysis, we examined the distribution of actin fibers during adipogenesis and identified the non-muscle myosin isoform (MYH10) as a potential cytoskeletal protein that may impact the function of adipocytes which led us to examine the role and function of MYH10 in adipocytes

Summary

Introduction

The process of adipocyte differentiation is termed adipogenesis. It is a well-coordinated process orchestrated by morphological and molecular changes in the cells and their niche. The cells undergo substantial morphological changes that are crucial for their commitment to a lineage-specific fate [3,4]. These changes are organized by cytoskeletal components responsible for determining and maintaining cellular shape and function and are a prerequisite for the induction of adipogenic signaling [5,6,7,8,9]. Cytoskeletal proteins are involved in the terminal differentiation phase and the insulin signaling pathway, where they are needed as a filament-based network for translocation of glucose transporter 4 (GLUT4) and other related processes [10,11,12,13,14,15]

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