当前位置： SCI文献检索 > JOURNAL OF CELL SCIENCE期刊下所有文献 > The calpain small subunit regulates cell-substrate mechanical interactions during fibroblast migration.

The calpain small subunit regulates cell-substrate mechanical interactions during fibroblast migration.

Abstract：

:Cell migration involves the dynamic formation and release of cell-substrate adhesions, where the exertion and detection of mechanical forces take place. Members of the calpain family of calcium-dependent proteases are believed to have a central role in these processes, possibly through the regulation of focal adhesion dynamics. The ubiquitous calpains, calpain 1 (mu-calpain) and calpain 2 (m-calpain), are heterodimers consisting of large catalytic subunits encoded by the Capn1 and Capn2 genes, respectively, and the small regulatory subunit encoded by Capn4. We have examined the role of the calpain regulatory small subunit in traction force production and mechanosensing during cell migration. Capn4-deficient or rescued cells were plated on flexible polyacrylamide substrates, for both the detection of traction forces and the application of mechanical stimuli. The total force output of Capn4-deficient cells was approximately 75% lower than that of rescued cells and the forces were more randomly distributed and less dynamic in Capn4-deficient cells than in rescued cells. Furthermore, Capn4-deficient cells were less adhesive than wild-type cells and they also failed to respond to mechanical stimulations by pushing or pulling the flexible substrate, or by engaging dorsal receptors to the extracellular matrix. Surprisingly, fibroblasts deficient in calpain 1 or calpain 2 upon siRNA-mediated knockdown of Capn1 or Capn2, respectively, did not show the same defects in force production or adhesion, although they also failed to respond to mechanical stimulation. Interestingly, stress fibers were aberrant and also contained fewer colocalised vinculin-containing adhesions in Capn4-deficient cells than Capn1- and Capn2-knockdown cells. Together, these results suggest that the calpain small subunit plays an important role in the production of mechanical forces and in mediating mechanosensing during fibroblast migration. Furthermore, the Capn4 gene product might perform functions secondary to, or independent of, its role as a regulatory subunit for calpain 1 and calpain 2.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Undyala VV,Dembo M,Cembrola K,Perrin BJ,Huttenlocher A,Elce JS,Greer PA,Wang YL,Beningo KA

doi

10.1242/jcs.036152

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

3581-8

issue

Pt 21

eissn

0021-9533

issn

1477-9137

pii

jcs.036152

journal_volume

121

pub_type

杂志文章

在线工具

The calpain small subunit regulates cell-substrate mechanical interactions during fibroblast migration.