Open Question The G protein connection: is it in the membrane or the cytoplasm?

The coupling, by G pro~ns, of membrane receptors to theu" effector protems ts often depicted as medg~ted by proteut-protem contacts m the hpgt btlayer of the membrane Ttus aracle argues that dus process revolves only an hydrophdzc domain of the receptor and develops entwe~ m the aqueous enwronment on the cytoplmmtc surface of the membrane G protems have ginned the status of quasi universal couplers between mem- brane receptors (R) of extracellular sig- nals, and membrane effectors (E) of various intracelinlar messengers Now- adays any report on a membrane trans- duct~on process, be it hormonal, neuronai, sensonal, nnmunolog~cai, chemotactle, or even a response to a growth or dLfferentmtlon factor, raises the questions which G protein is involved, to which effector is ~t coupled ~ G proteins control the actwity not only of adenylate cyclases and cGMP phos- phodlesterases LPDE), but also that of phosphatidyhnosltol 4,5-blsphosphate (PIPz) specdic phosphohpase C (PLC) They may even regulate directly the con- ductance of some ionic channels I-s This universal 'G protein connection' is often illustrated by diagrams in which two parallel lines symbolize the cell membrane; they represent the polar head surfaces of the hpids, which are the boundanes to the hydrophoblc layer of the membrane Symbolic detmls, such as the hpld paraffin chains, may be added The proteins, tittle bubbles or more elaborate geometnc shapes, float on, or more often sink, panmily or even totally, in the paraffin layer Sometimes it even looks as if they shuttle transversaily across the bdayer, between the receptor on the extmcellular surface and the effectors on the cytoplasnuc surface ~ Such schemes are not, of course, meant to give accurate structural descriptions of the molecular organLza- tlon of the system They are, however, not innocent they reflect and mfluence our ways of thinking In most schemes,