Wnt5a/Ca2+ signal promotes myogenic differentiation by mediating a slow and sustained influx of Ca2+

Abstract

The extracellular Ca 2+ is crucial for the regeneration of skeletal muscles, but there is still uncertainty regarding the channels through which it enters the cells. The purpose of this study is to investigate how the Wnt5a/Ca²⁺ signaling pathway promotes myogenic differentiation by regulating which calcium channels on the cell membrane. Myogenic regulatory factors (MRFs) play an important regulatory role in the occurrence and development of skeletal muscle, while overexpression or knockdown of Wnt5a can affect the expression levels of MRFs. Increased expression of Wnt5a resulted in significant increase of intracellular Ca 2+ levels, and knockdown of TRPC3 could partially reverse the effect of Wnt5a. This indicates that in addition to the TRPC3 channel, there are other Ca 2+ channels involved in the process of transporting extracellular Ca 2+ into the cells. When we treated with verapamil, we found that it could significantly reduce the level of Ca 2+ entering the cells, indicating that this unknown Ca 2+ channel is a slow calcium channel. Through co-immunoprecipitation, we found that Ca V 1.1 was abundantly accumulated in the TRPC3 pull-down complex, indicating that this slow calcium channel is Ca V 1.1, and the expression of Ca V 1.1 is influenced by TRPC3. In simple terms, the activated TRPC3 activates Ca v 1.1, inducing a slow and sustained inward flow of extracellular Ca 2+ , leading to the increase of intracellular levels of Ca 2+ , and finally promote myogenic differentiation.