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Pannexin 1 regulates skeletal muscle regeneration by promoting bleb-based myoblast migration and fusion through a novel lipid based signaling mechanism

Suarez-Berumen, Katia, Collins-Hooper, Henry, Gromova, Anastasia, Meech, Robyn, Sacco, Alessandra, Dash, Phil R., Mitchell, Robert, Shestopalov, Valery I., Woolley, Thomas, Vaiyapuri, Sakthivel, Patel, Ketan and Makarenkova, Helen P. 2021. Pannexin 1 regulates skeletal muscle regeneration by promoting bleb-based myoblast migration and fusion through a novel lipid based signaling mechanism. Frontiers in Cell and Developmental Biology 9 , 736813. 10.3389/fcell.2021.736813

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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 that Panx1–/– 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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Mathematics
Subjects: Q Science > QA Mathematics
Q Science > QH Natural history > QH301 Biology
Additional Information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
Publisher: Frontiers Media
ISSN: 2296-634X
Date of First Compliant Deposit: 20 September 2021
Date of Acceptance: 13 September 2021
Last Modified: 20 Oct 2021 14:08
URI: http://orca.cardiff.ac.uk/id/eprint/144147

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