PHAR 5091.004

Course Name: Cell Membrane Microdomains and Signaling

Course Director: Dr. William Clarke

Course Content:

The cell membrane is composed of microdomains that are characterized by their unique protein and lipid composition and that are thought to serve specialized roles in protein trafficking and signal transduction. This course will provide students with an understanding of the structure and role of membrane microdomains as related to 7-transmembrane spanning (G protein-coupled) receptor signaling. The course will emphasize the experimental approaches and interpretation of data.

1. Graeser D and Neubig RR (1993) Compartmentation of receptors and guanine nucleotide-binding proteins in NG108-15 cells: lack of cross-talk in agonist binding among the alpha 2-adrenergic, muscarinic, and opiate receptors. Mol Pharmacol 43:434-443.
2. Kwon G, Axelrod D and Neubig RR (1994) Lateral mobility of tetramethylrhodamine (TMR) labelled G protein alpha and beta gamma subunits in NG 108-15 cells. Cell Signal 6:663-679.
3. Johnson BD, Scheuer T and Catterall WA (1994) Voltage-dependent potentiation of L-type Ca2+ channels in skeletal muscle cells requires anchored cAMP-dependent protein kinase. Proc Natl Acad Sci U S A 91:11492-11496.
4. Field KA, Holowka D and Baird B (1997) Compartmentalized activation of the high affinity immunoglobulin E receptor within membrane domains. J Biol Chem 272:4276-4280.
5. Carman CV, Lisanti MP and Benovic JL (1999) Regulation of G protein-coupled receptor kinases by caveolin. J Biol Chem 274:8858-8864.
6. Schreiber S, Fleischer J, Breer H and Boekhoff I (2000) A possible role for caveolin as a signaling organizer in olfactory sensory membranes. J Biol Chem 275:24115-24123.
7. Sowa G, Pypaert M and Sessa WC (2001) Distinction between signaling mechanisms in lipid rafts vs. caveolae. Proc Natl Acad Sci U S A 98:14072-14077.
8. Delmas P, Wanaverbecq N, Abogadie FC, Mistry M and Brown DA (2002) Signaling microdomains define the specificity of receptor-mediated InsP(3) pathways in neurons. Neuron 34:209-220.
9. Yamabhai M and Anderson RG (2002) Second Cysteine-rich Region of Epidermal Growth Factor Receptor Contains Targeting Information for Caveolae/Rafts. J Biol Chem 277:24843-24846.
10. Xiang Y, Rybin VO, Steinberg SS and Kobilka B (2002) Caveolar localization dictates physiologic signaling of beta2 adrenoceptors in neonatal cardiac myocytes. J Biol Chem.

Grading: Students will read each paper and discuss critically the content of each paper with the course director. For each paper, the student will provide a brief (one page, double spaced) report highlighting the paper's strengths and weaknesses and presenting its important findings and their significance with respect to receptor-mediated signal transduction. It is expected that students will do some additional reading of the primary literature as needed to familiarize themselves with the paper under discussion. Students will be graded based upon the one-page summaries and the quality of discussions of the papers with the course director. Grading will be on a lettered scale.

Pre-requisites: Principles of Pharmacology

Credit Hours: 1 credit

When offered: Anytime