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The role of mechanical tension on lipid raft dependent PDGF-induced TRPC6 activation.

Abstract：

:Canonical transient receptor potential channel 6 (TRPC6) can play an important role in governing how cells perceive the surrounding material environment and regulate Ca(2+) signaling. We have designed a TRPC6 reporter based on fluorescence resonance energy transfer (FRET) to visualize the TRPC6-mediated calcium entry and hence TRPC6 activity in live cells with high spatiotemporal resolutions. In mouse embryonic fibroblasts (MEFs), platelet-derived growth factor BB (PDGF) can activate the TRPC6 reporter, mediated by phospholipase C (PLC). This TRPC6 activation occurred mainly at lipid rafts regions of the plasma membrane because disruption of lipid raft/caveolae by methyl-β-cyclodextrin (MβCD) or the expression of dominant-negative caveolin-1 inhibited the TRPC6 activity. Culturing cells on soft materials or releasing the intracellular tension by ML-7 reduced this PDGF-induced activation of TRPC6 without affecting the PDGF-regulated Src or inositol 1,4,5-trisphosphate (IP3) receptor function, suggesting a specific role of mechanical tension in regulating TRPC6. We further showed that the release of intracellular tension had similar effect on the diffusion coefficients of TRPC6 and a raft marker, confirming a strong coupling between TRPC6 and lipid rafts. Therefore, our results suggest that the TRPC6 activation mainly occurs at lipid rafts, which is regulated by the mechanical cues of surrounding materials.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Lei L,Lu S,Wang Y,Kim T,Mehta D,Wang Y

doi

10.1016/j.biomaterials.2013.12.030

subject

Has Abstract

pub_date

2014-03-01 00:00:00

pages

2868-77

issue

9

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(13)01514-7

journal_volume

35

pub_type

杂志文章

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