The human serotonin1A receptor exhibits G-protein-dependent cell surface dynamics.
Seven transmembrane domain G-protein-coupled receptors constitute the largest family of proteins in mammals. Signal transduction events mediated by such receptors are the primary means by which cells communicate with and respond to their external environment. The major paradigm in this signal transduction process is that stimulation of the receptor leads to the recruitment and activation of heterotrimeric GTP-binding proteins. These initial events, which are fundamental to all types of G-protein-coupled receptor signaling, occur at the plasma membrane via protein-protein interactions. As a result, the dynamics of the activated receptor on cell surfaces represents an important determinant in its encounter with G-proteins, and has significant impact on the overall efficiency of the signal transduction process. We have monitored the cell surface dynamics of the serotonin(1A) receptor, an important member of the G-protein-coupled receptor superfamily, in relation to its interaction with G-proteins. Fluorescence recovery after photobleaching experiments carried out with the receptor tagged to the enhanced yellow fluorescent protein indicate that G-protein activation alters the diffusion properties of the receptor in a manner suggesting the activation process leads to dissociation of G-proteins from the receptor. This result demonstrates that the cell surface dynamics of the serotonin(1A) receptor is modulated in a G-protein-dependent manner. Importantly, this result could provide the basis for a sensitive and powerful approach to assess receptor/G-protein interaction in an intact cellular environment.
Pucadyil
Thomas J
TJ
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
Chattopadhyay
Amitabha
A
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004058:Diffusion; D036681:Fluorescence Recovery After Photobleaching; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D044282:Receptor, Serotonin, 5-HT1A; D020962:Heterotrimeric GTP-Binding Proteins