Accessibility navigation


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

Suarez-Berumen, K., Collins-Hooper, H., Gormova, A., Meech, R., Sacco, A., Dash, P., Mitchell, R., Shestopalov, V., Woolley, T., Vaiyapuri, S. ORCID: https://orcid.org/0000-0002-6006-6517, Patel, K. and Makarenkova, H. (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. 736813. ISSN 2296-634X

[img]
Preview
Text (Open Access) - Published Version
· Available under License Creative Commons Attribution.
· Please see our End User Agreement before downloading.

8MB
[img] Text - Accepted Version
· Restricted to Repository staff only

5MB

It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.3389/fcell.2021.736813

Abstract/Summary

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
Refereed:Yes
Divisions:Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:100158
Publisher:Frontiers

Downloads

Downloads per month over past year

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation