Format

Send to

Choose Destination
J Cell Physiol. 2015 Sep;230(9):2086-97. doi: 10.1002/jcp.24936.

Mechanosensitive store-operated calcium entry regulates the formation of cell polarity.

Author information

1
Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
2
Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
3
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
4
Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan.
5
Department of Pharmacology, National Cheng Kung University, Tainan, Taiwan.
6
Medical Device Innovation Center, National Cheng Kung University, Tainan, Taiwan.

Abstract

Ca(2+) -mediated formation of cell polarity is essential for directional migration which plays an important role in physiological and pathological processes in organisms. To examine the critical role of store-operated Ca(2+) entry, which is the major form of extracellular Ca(2+) influx in non-excitable cells, in the formation of cell polarity, we employed human bone osteosarcoma U2OS cells, which exhibit distinct morphological polarity during directional migration. Our analyses showed that Ca(2+) was concentrated at the rear end of cells and that extracellular Ca(2+) influx was important for cell polarization. Inhibition of store-operated Ca(2+) entry using specific inhibitors disrupted the formation of cell polarity in a dose-dependent manner. Moreover, the channelosomal components caveolin-1, TRPC1, and Orai1 were concentrated at the rear end of polarized cells. Knockdown of TRPC1 or a TRPC inhibitor, but not knockdown of Orai1, reduced cell polarization. Furthermore, disruption of lipid rafts or overexpression of caveolin-1 contributed to the downregulation of cell polarity. On the other hand, we also found that cell polarity, store-operated Ca(2+) entry activity, and cell stiffness were markedly decreased by low substrate rigidity, which may be caused by the disorganization of actin filaments and microtubules that occurs while regulating the activity of the mechanosensitive TRPC1 channel.

PMID:
25639747
DOI:
10.1002/jcp.24936
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center