title: A sphingosine-1-phosphate-activated calcium channel controlling vascular smooth muscle cell motility.
abstract: In a screen of potential lipid regulators of transient receptor potential (TRP) channels, we identified sphingosine-1-phosphate (S1P) as an activator of TRPC5. We explored the relevance to vascular biology because S1P is a key cardiovascular signaling molecule. TRPC5 is expressed in smooth muscle cells of human vein along with TRPC1, which forms a complex with TRPC5. Importantly, S1P also activates the TRPC5-TRPC1 heteromultimeric channel. Because TRPC channels are linked to neuronal growth cone extension, we considered a related concept for smooth muscle. We find S1P stimulates smooth muscle cell motility, and that this is inhibited by E3-targeted anti-TRPC5 antibody. Ion permeation involving TRPC5 is crucial because S1P-evoked motility is also suppressed by the channel blocker 2-aminoethoxydiphenyl borate or a TRPC5 ion-pore mutant. S1P acts on TRPC5 via two mechanisms, one extracellular and one intracellular, consistent with its bipolar signaling functions. The extracellular effect appears to have a primary role in S1P-evoked cell motility. The data suggest S1P sensing by TRPC5 calcium channel is a mechanism contributing to vascular smooth muscle adaptation.
authors: Institute of Membrane and Systems Biology, University of Leeds, Leeds, LS2 9JT, UK.
authors: Shang-Zhong
authors: SZ
authors: Xu
authors: Katsuhiko
authors: K
authors: Muraki
authors: Fanning
authors: F
authors: Zeng
authors: Jing
authors: J
authors: Li
authors: Piruthivi
authors: P
authors: Sukumar
authors: Samir
authors: S
authors: Shah
authors: Alexandra M
authors: AM
authors: Dedman
authors: Philippa K
authors: PK
authors: Flemming
authors: Damian
authors: D
authors: McHugh
authors: Jacqueline
authors: J
authors: Naylor
authors: Alex
authors: A
authors: Cheong
authors: Alan N
authors: AN
authors: Bateson
authors: Christopher M
authors: CM
authors: Munsch
authors: Karen E
authors: KE
authors: Porter
authors: David J
authors: DJ
authors: Beech