Polycystin-2 Is Required for Starvation- and Rapamycin-Induced Atrophy in Myotubes

Abstract

Muscle atrophy involves a massive catabolism of intracellular components leading to a significant reduction in cellular and tissue volume. In this regard, autophagy, an intracellular mechanism that degrades proteins and organelles, has been implicated with muscle breakdown. Recently, it has shown that polycystin-2 (PC2), a membrane protein that belongs to the transient receptor potential (TRP) family, is required for the maintenance of cellular proteostasis, by regulating autophagy in several cell types. The role of PC2 in the control of atrophy and autophagy in skeletal muscle remains unknown. Here, we show that PC2 is required for the induction of atrophy in C2C12 myotubes caused by nutrient deprivation or rapamycin exposure. Consistently, overexpression of PC2 induces atrophy in C2C12 myotubes as indicated by decreasing of the myogenic proteins myogenin and caveolin-3. In addition, we show that inhibition of mTORC1, by starvation or rapamycin is inhibited in cells when PC2 is silenced. Importantly, even if PC2 regulates mTORC1, our results show that the regulation of atrophy by PC2 is independent of autophagy. This study provides novel evidence regarding the role of PC2 in skeletal muscle cell atrophy.

Cardiovascular perspectives of the TRP channel polycystin 2

“…In addition to PC2 enabling the regulation of the intracellular calcium release apparatus, ER-localized PC2, together with its partner protein PC1, which can localize to the mitochondria, can facilitate calcium exchange in organellar contact sites between the ER and mitochondria (Chiaravalli et al, 2016;Padovano et al, 2017;Rowe et al, 2013;Torres et al, 2019). Consistent with the effect of PC2 on cellular metabolism, PC2 regulates the autophagic pathway in myoblasts and cardiomyocytes (Criollo et al, 2018;Kretschmar et al, 2019;Peña-Oyarzun et al, 2017). In C2C12 myoblasts, calcium appears to be essential for the conversion of myoblasts to fused cells and ultimately for the maturation of an ER structure to a more sarcoplasmic structure (Márquez-Nogueras et al, 2022).…”

Intermittent Starvation Promotes Maturation of Human Embryonic Stem Cell-Derived Cardiomyocytes

“…Despite a lack of knowledge regarding the regulatory mechanism, the prenatal-to-postnatal transition is believed to present a critical window for cardiomyocyte maturation (Neary et al, 2014;Gentillon et al, 2019). Immediately after birth, neonates sustain severe nutrient starvation and display massive autophagosome formation in their hearts, indicating a critical role of autophagy during heart development (Correia et al, 2017;Kretschmar et al, 2019). Our approach in this study is to mimic the in vivo starvation event through EBSS treatment to promote hESC-CM maturation.…”