ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation.
Publication/Presentation Date
4-10-2018
Abstract
Focal adhesions anchor cells to extracellular matrix (ECM) and direct assembly of a pre-stressed actin cytoskeleton. They act as a cellular sensor and regulator, linking ECM to the nucleus. Here, we identify proteolytic turnover of the anti-adhesive proteoglycan versican as a requirement for maintenance of smooth muscle cell (SMC) focal adhesions. Using conditional deletion in mice, we show that ADAMTS9, a secreted metalloprotease, is required for myometrial activation during late gestation and for parturition. Through knockdown of ADAMTS9 in uterine SMC, and manipulation of pericellular versican via knockdown or proteolysis, we demonstrate that regulated pericellular matrix dynamics is essential for focal adhesion maintenance. By influencing focal adhesion formation, pericellular versican acts upstream of cytoskeletal assembly and SMC differentiation. Thus, pericellular versican proteolysis by ADAMTS9 balances pro- and anti-adhesive forces to maintain an SMC phenotype, providing a concrete example of the dynamic reciprocity of cells and their ECM.
Volume
23
Issue
2
First Page
485
Last Page
498
ISSN
2211-1247
Published In/Presented At
Mead, T. J., Du, Y., Nelson, C. M., Gueye, N. A., Drazba, J., Dancevic, C. M., Vankemmelbeke, M., Buttle, D. J., & Apte, S. S. (2018). ADAMTS9-Regulated Pericellular Matrix Dynamics Governs Focal Adhesion-Dependent Smooth Muscle Differentiation. Cell reports, 23(2), 485–498. https://doi.org/10.1016/j.celrep.2018.03.034
Disciplines
Medicine and Health Sciences
PubMedID
29642006
Department(s)
Department of Obstetrics and Gynecology
Document Type
Article