Lipid droplets contribute myogenic differentiation in C2C12 by promoting the remodeling of the acstin-filament

Yanjie Tan,Zhuqing Ren,Yi Jin,Jian Wu,Pengxiang Zhao

doi:10.1038/s41419-021-04273-8

Abstract

Lipid droplet (LD), a multi-functional organelle, is found in most eukaryotic cells. LDs participate in the regulation of many cellular processes including proliferation, stress, and apoptosis. Previous studies showed the athlete’s paradox that trained athletes accumulate LDs in their skeletal muscle. However, the impact of LDs on skeletal muscle and myogenesis is not clear. We discovered that C2C12 myoblast cells containing more LDs formed more multinucleated muscle fibers. We also discovered that LDs promoted cell migration and fusion by promoting actin-filaments remodeling. Mechanistically, two LD-proteins, Acyl-CoA synthetase long chain family member 3 (ACSL3) and lysophosphatidylcholine acyltransferase 1 (LPCAT1), medicated the recruitment of actinin proteins which contributed to actin-filaments formation on the surface of LDs. During remodeling, the actinin proteins on LDs surface translocated to actin-filaments via ARF1/COPI vesicles. Our study demonstrate LDs contribute to cell differentiation, which lead to new insight into the LD function.

Highlights

Lipid droplets (LDs) are multi-functional organelles in the cell [1], consisting of a neutral lipid core and a monolayer of phospholipid membranes
LDs promote myoblast to form multinucleated myotubes To determine whether LDs play a role in myogenesis, we examined the formation of multinucleated myotubes in C2C12
The results showed that the A, C, E, and F fragments could bind to Acyl-CoA synthetase long chain family member 3 (ACSL3) and lysophosphatidylcholine acyltransferase 1 (LPCAT1), which indicated the SR domain was the key protein domain for ACTN3 binding to ACSL3 and LPCAT1 (Fig. 4B)

Summary

INTRODUCTION

Lipid droplets (LDs) are multi-functional organelles in the cell [1], consisting of a neutral lipid core and a monolayer of phospholipid membranes. LDs provide necessary lipid components to cell proliferation including synthesis of membranes and production of metabolic energy [8,9,10]. LDs interact with the endoplasmic reticulum to regulate cellular lipid synthesis [6]. The contact between LDs and the endoplasmic reticulum and the formation of “lipidic bridges” allows the phospholipid membrane of LDs to link to the outer membrane of the endoplasmic reticulum [11] Many proteins, such as triglyceride synthases (DGAT2 and GPAT4), are transferred from the endoplasmic reticulum to the LD surface due to the fluidity of the membrane, which accelerates the growth of LDs and allows them to store more lipids [6]. Our results suggest the potential link between LDs and muscle development and injury-regeneration

MATERIALS AND METHODS

RESULTS

DISCUSSION