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E-Conference: Defining Calcium Entry Signals

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GTP-gamma(S), small G-proteins, and SOC- Any connection?

7 June 2004

Peter J Lockyer

Considering Rho is fine, but I would suggest there are a couple of other more interesting groups of small GTPases.

I would say, having recently spoken to Alan Dawson who first discovered the GTP effect (reported in FEBS 1985), that much is probably due to the regulation of ER integrity and continuity, which would include cytoskeletal remodelling via Rho, but may be more pertinent to Rabs and Arfs. Alan would be a much better source of information than me, and so would Jim and Gary Bird.

Using RNAi would seem a simple method to start having a look, but imagine the number of indirect effects this would produce on agonist-induced calcium entry, e.g. receptor numbers, receptor trafficking, phosphoinositide levels, you name it really.

Ras is very often upstream of Rho family member activation and there are very specific influences of oncogenic Ras on bradykinin-induced calcium entry - all in transformed NIH3T3 cells first reported by Hans H Grunicke (and later others). From my perspective, Ras is one of the most interesting small GTPases to look at because there are 2 specific calcium sensors (CAPRI and RASAL) that regulate Ras activity. There is nothing quite so specific and dynamic for any other small GTPase.

I would say that yes, small GTPases must be involved in the regulated of SOCE. At multiple levels, probably mainly indirect. So the question is how to delineate all the indirect effects, and whether this is possible considering the number of small GTPases that could be involved; upstream and downstream of each other.

BTW, I haven't noticed obvious effects of CAPRI on calcium signalling, so this is a neat tool but with negative results (for Ras).

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