Pannexin 1 Regulates Skeletal Muscle Regeneration by Promoting Bleb-Based Myoblast Migration and Fusion Through a Novel Lipid Based Signaling Mechanism
Abstract
Adult skeletal muscle has robust regenerative capabilities due to the presence of a resident stem cell population called satellite cells. Muscle injury leads to these normally quiescent cells becoming molecularly and metabolically activated and embarking on a program of proliferation, migration, differentiation, and fusion culminating in the repair of damaged tissue. These processes are highly coordinated by paracrine signaling events that drive cytoskeletal rearrangement and cell-cell communication. Pannexins are a family of transmembrane channel proteins that mediate paracrine signaling by ATP release. It is known that Pannexin1 (Panx1) is expressed in skeletal muscle, however, the role of Panx1 during skeletal muscle development and regeneration remains poorly understood. Here we show that Panx1 is expressed on the surface of myoblasts and its expression is rapidly increased upon induction of differentiation and thatPanx1–/–mice exhibit impaired muscle regeneration after injury.Panx1–/–myoblasts activate the myogenic differentiation program normally, but display marked deficits in migration and fusion. Mechanistically, we show that Panx1 activates P2 class purinergic receptors, which in turn mediate a lipid signaling cascade in myoblasts. This signaling induces bleb-driven amoeboid movement that in turn supports myoblast migration and fusion. Finally, we show that Panx1 is involved in the regulation of cell-matrix interaction through the induction of ADAMTS (Disintegrin-like and Metalloprotease domain with Thrombospondin-type 5) proteins that help remodel the extracellular matrix. These studies reveal a novel role for lipid-based signaling pathways activated by Panx1 in the coordination of myoblast activities essential for skeletal muscle regeneration.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 05, 2021
- Source ID
- 10.3389/fcell.2021.736813
Entities
People
- Alessandra Sacco
- Anastasia Gromova
- Helen P. Makarenkova
- Henry Collins-hooper
- Katia Suarez-berumen
- Ketan Patel
- Phil R. Dash
- Robert J Mitchell
- Robyn Meech
- Sakthivel Vaiyapuri
- Thomas E. Woolley
- Valery I. Shestopalov
Organizations
- Biotechnology and Biological Sciences Research Council
- Freiburg Institute for Advanced Studies
- French Muscular Dystrophy Association
- National Eye Institute
- Russian Science Foundation
- United States Department of Defense