Dopamine and Calcium Signal Interactions in the Developing Striatum: Control by Kinetics of CREB Phosphorylation

Abstract

The concentration of dopamine- and Ca 2+ -related signaling molecules in the striatum during development renders the developing striatum an attractive model system for studying the interactions between these two plasticity-related systems during development. It is likely that gene regulation mediated by dopamine and Ca 2+ signals is one of the molecular bases of neuronal plasticity and development. This issue has been approached by analyzing regulation of the cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB). CREB is a transcription factor that is an important mediator in the plasticity underlying memory in both the invertebrate and vertebrate systems. Activation of CREB can occur through phosphorylation of CREB on its residue by cAMP dependent protein kinase or by Ca 2+ influx through voltage-sensitive Ca 2+ channels. Activated CREB can subsequently regulate cAMP-response element (CRE)-containing genes through the CRE. Accordingly, CREB has been proposed to be a convergence molecule for CAMP- and Ca 2+ -mediated activation. As dopamine D1-class receptors are linked to the cAMP-adenylate cyclase pathway, dopamine and Ca 2+ signals may share a common transduction pathway through CREB in regulating striatal gene expression. This chapter reviews findings suggesting that the kinetics of CREB phosphorylation may be a critical factor in determining downstream gene activation by dopamine and Ca 2+ in the developing striatum.