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22 pages, 4016 KiB

Open AccessEditor’s ChoiceArticle

Characterization of the Skeletal Muscle Secretome Reveals a Role for Extracellular Vesicles and IL1α/IL1β in Restricting Fibro/Adipogenic Progenitor Adipogenesis

by Simone Vumbaca, Giulio Giuliani, Valeria Fiorentini, Flavia Tortolici, Andrea Cerquone Perpetuini, Federica Riccio, Simona Sennato, Cesare Gargioli, Claudia Fuoco, Luisa Castagnoli and Gianni Cesareni

Biomolecules 2021, 11(8), 1171; https://doi.org/10.3390/biom11081171 - 08 Aug 2021

Cited by 9 | Viewed by 3830

Abstract

Repeated mechanical stress causes injuries in the adult skeletal muscle that need to be repaired. Although muscle regeneration is a highly efficient process, it fails in some pathological conditions, compromising tissue functionality. This may be caused by aberrant cell–cell communication, resulting in the deposition of fibrotic and adipose infiltrates. Here, we investigate in vivo changes in the profile of skeletal muscle secretome during the regeneration process to suggest new targetable regulatory circuits whose failure may lead to tissue degeneration in pathological conditions. We describe the kinetic variation of expression levels of 76 secreted proteins during the regeneration process. In addition, we profile the gene expression of immune cells, endothelial cells, satellite cells, and fibro-adipogenic progenitors. This analysis allowed us to annotate each cell-type with the cytokines and receptors they have the potential to synthetize, thus making it possible to draw a cell–cell interaction map. We next selected 12 cytokines whose receptors are expressed in FAPs and tested their ability to modulate FAP adipogenesis and proliferation. We observed that IL1α and IL1β potently inhibit FAP adipogenesis, while EGF and BTC notably promote FAP proliferation. In addition, we characterized the cross-talk mediated by extracellular vesicles (EVs). We first monitored the modulation of muscle EV cargo during tissue regeneration. Using a single-vesicle flow cytometry approach, we observed that EVs differentially affect the uptake of RNA and proteins into their lumen. We also investigated the EV capability to interact with SCs and FAPs and to modulate their proliferation and differentiation. We conclude that both cytokines and EVs secreted during muscle regeneration have the potential to modulate adipogenic differentiation of FAPs. The results of our approach provide a system-wide picture of mechanisms that control cell fate during the regeneration process in the muscle niche. Full article

(This article belongs to the Special Issue State-of-the-Art of Myology in Italy 2020–2021)

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27 pages, 3494 KiB

Open AccessFeature PaperEditor’s ChoiceReview

The Sarcoplasmic Reticulum of Skeletal Muscle Cells: A Labyrinth of Membrane Contact Sites

by Daniela Rossi, Enrico Pierantozzi, David Osamwonuyi Amadsun, Sara Buonocore, Egidio Maria Rubino and Vincenzo Sorrentino

Biomolecules 2022, 12(4), 488; https://doi.org/10.3390/biom12040488 - 23 Mar 2022

Cited by 7 | Viewed by 9339

Abstract

The sarcoplasmic reticulum of skeletal muscle cells is a highly ordered structure consisting of an intricate network of tubules and cisternae specialized for regulating Ca²⁺ homeostasis in the context of muscle contraction. The sarcoplasmic reticulum contains several proteins, some of which support Ca²⁺ storage and release, while others regulate the formation and maintenance of this highly convoluted organelle and mediate the interaction with other components of the muscle fiber. In this review, some of the main issues concerning the biology of the sarcoplasmic reticulum will be described and discussed; particular attention will be addressed to the structure and function of the two domains of the sarcoplasmic reticulum supporting the excitation–contraction coupling and Ca²⁺-uptake mechanisms. Full article

(This article belongs to the Special Issue State-of-the-Art of Myology in Italy 2020–2021)

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14 pages, 1494 KiB

Open AccessEditor’s ChoiceReview

The Builders of the Junction: Roles of Junctophilin1 and Junctophilin2 in the Assembly of the Sarcoplasmic Reticulum–Plasma Membrane Junctions in Striated Muscle

by Stefano Perni

Biomolecules 2022, 12(1), 109; https://doi.org/10.3390/biom12010109 - 10 Jan 2022

Cited by 8 | Viewed by 2839

Abstract

Contraction of striated muscle is triggered by a massive release of calcium from the sarcoplasmic reticulum (SR) into the cytoplasm. This intracellular calcium release is initiated by membrane depolarization, which is sensed by voltage-gated calcium channels Ca_V1.1 (in skeletal muscle) and Ca_V1.2 (in cardiac muscle) in the plasma membrane (PM), which in turn activate the calcium-releasing channel ryanodine receptor (RyR) embedded in the SR membrane. This cross-communication between channels in the PM and in the SR happens at specialized regions, the SR-PM junctions, where these two compartments come in close proximity. Junctophilin1 and Junctophilin2 are responsible for the formation and stabilization of SR-PM junctions in striated muscle and actively participate in the recruitment of the two essential players in intracellular calcium release, Ca_V and RyR. This short review focuses on the roles of junctophilins1 and 2 in the formation and organization of SR-PM junctions in skeletal and cardiac muscle and on the functional consequences of the absence or malfunction of these proteins in striated muscle in light of recently published data and recent advancements in protein structure prediction. Full article

(This article belongs to the Special Issue State-of-the-Art of Myology in Italy 2020–2021)

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