How do GPCRs transmit a signal across the plasma membrane?

Question

How do G-coupled protein receptors (GPCR) transmit signals through the plasma membrane?

Links containing information about this and pictures will be very helpful.

Answer 1

The G-coupled protein receptors (GPCR) transmit signals from outside of the cell into the cell and activate downstream signalling pathways. These change for example the expression of certain genes.

The whole process is a coorperation between the receptor, a G-protein, GTP as a co-factor and the ligand of the receptor (which starts the whole process). An extensive description (including much more images) is available in the Wikipedia, but in short, it looks like the images below (from the Wikipedia article on GPCR):

To answer how this signal is tranferred from the outside to the inside look at the first image: Upon ligand binding the conformation of the receptor changes its conformation and brings some of it transmembrane helices together so the G$\alpha$ subunit can bind here and activate downstream signalling.

The whole process happens in a few steps:

1. In the resting state the receptor has a trimeric G-protein (consisting of the subunits $\alpha, \beta$ and $\gamma$ bound on its cytosolic site. The G-protein also has a GDP molecule bound to it $\alpha$ subunit.
2. Upon binding of the ligand, the receptor changes its conformation, and G$\alpha$ exchanges the GD against GTP, which activates the complex.
3. The G-protein dissociates into the active G$\alpha$ the G$\beta\gamma$ subunits, which signal to downstream signal transduction pathways like the MAP-Kinase pathway.
4. Binding of RGS (regulator of G-protein signalling) to the g$\alpha$ subunit activates the intrinsic GTPase function of the subunit and hydrolyses GTP into GDP and P. The GDP stays bound to the G$\alpha$ subunit, which changes its conformation and forms the G-protein trimer at the receptor. At the receptor itself this induces also a change in conformation which makes the ligand dissociate from the receptor.

At the end of the fourth step the receptor has returned into its inactive form and stays there until the next ligand binding.