GPCR signaling mediated by PDZ-GEFs during development and in adult central nervous system signaling

Wednesday, November 06, 2013 — Concurrent Symposia Session I
12:30 p.m. – 2:30 p.m.	FAES Academic Center lower-level Classroom 4

Chair

Lee Eiden, NIMH

Program

This symposium topic is timely because PDZ-Rapgefs have been implicated in development for some time, but only in the past year has it been appreciated that they are also sensors for cAMP, and are activated through G-protein coupled receptor (GPCR) occupancy by both biogenic amines (e.g. dopamine) and neuropeptides (e.g. PACAP and VIP). The symposium is of broad interest to: developmental biologists, because of the critical role of Rapgef2 in both hematopoiesis and cortical neuronal development; neurobiologists and neuroendocrinologists, because PDZ-Rapgef signaling is at this time the sole known mode of cAMP-dependent activation of ERK, a MAPK critical for neuronal plasticity underlying learning and memory and transduction of stress signaling via the HPA axis; neuropharmacologists and translational scientists, because cell lines incorporating expression of Rapgef2 will provide an additional dimension to GPCR high-throughput screening critical for obtaining needed CNS-active drugs.

New perspectives on cAMP signaling-protein kinase A, Epac1/2, and neuritogenic cAMP sensor (NCS)/Rapgef2 are a triumvirate of cAMP sensors that parcellate third messenger signaling in mammals
Lee Eiden, NIMH

Molecular and genetic study of Rapgef2 in drosophila and mice
Steve Hou, NCI

NCS/Rapgef2: Why GPCR-Gs activation of ERK is specific to neuron and endocrine cells
Andrew Emery, NIMH

Neuropeptide signaling to ERK in CNS neurons mediating stress responses
Tomris Mustafa, NIMH

D1 dopamine receptor signaling to ERK: New substrates for understanding dopamine receptor supersensitivity underlying dopamine-dependent dyskinesias
Chip Gerfen, NIMH