Lateral mobility of proteins and lipids in the red cell membrane and the activation of adenylate cyclase by β‐adrenergic receptors

Abstract

Models of /?-adrenergic signal transduction in red blood cell membranes frequently assume that at least one of the membrane-bound components is laterally mobile and distributes the hormonal signal in the membrane plane. However, direct measurements reveal that protein lateral mobility in the red cell membrane is severely restricted. Furthermore, the spectrin-actin skeleton compartmentalizes the cytoplasmic face of the red cell membrane into a regular array of small elementary areas. These considerations support models in which the /?-adrenergic signal is spread in the membrane plane by a molecule which has binding sites on the membrane but diffuses in the aqueous compartment,

G-Protein-Dependent Cell Surface Dynamics of the Human Serotonin1A Receptor Tagged to Yellow Fluorescent Protein

“…Persistent activation of the receptor with agonists, as is the case in our experiments, would on average tend to reduce the fraction of receptors interacting with G-proteins as has been recently shown (55). The presence of AlF 4 -would lock the GR subunits in an active state, similar to a GTP-γ-S bound GR subunit, preventing them from associating with the receptor (47,48) and thereby increasing the fraction of receptors uncoupled to G-proteins. The treatment of cells with pertussis toxin would inactivate the existing pool of G-proteins and increase the fraction of receptors uncoupled to G-proteins (56).…”

“…An important consequence of this is that the dynamics of the activated receptor on the cell surface represents an important determinant in its encounter with G-proteins and has significant impact on the overall efficiency of the signal transduction process. This aspect forms the basis of the "mobile receptor" hypothesis in which the lateral mobility of the receptor on the cell surface is assumed to play an important role in cellular signaling (4). This model proposes that receptor-effector interactions at the plasma membrane are controlled by lateral mobility of the interacting components.…”

The human serotonin1A receptor exhibits G-protein-dependent cell surface dynamics

“…These initial events, fundamental to all types of GPCR signaling, occur at the plasma membrane via protein-protein interactions. An important consequence of this is that the dynamics of the activated receptor on the cell surface represents an important determinant in its encounter with G-proteins, and has significant impact on the overall efficiency of the signal transduction process [6]. In this context, the cell surface organization of GPCRs and Gproteins participating in this signal transduction process assumes relevance.…”

Lateral mobility of the phospholipase C-activating vasopressin V1-type receptor in A7r5 smooth muscle cells: a comparison with the adenylate cyclase-coupled V2-receptor.

“…Recent data from the ,Badrenergic receptor -adenylate cyclase (Ransnas and Insel, 1988;Ransnas et al, 1989) and other (Stryer and Bourne, 1986;Lynch et al, 1986;McAndle et al, 1988) systems indicate that agonist binding to receptor promotes the redistribution of the Gs,, into the cytosolic fraction. This implies that receptor lateral diffusion-mediated interaction with G-proteins may be the rate-limiting step in signal transduction, all subsequent events occurring more rapidly in the aqueous phase (Peters, 1988;Chabre, 1987).…”