A CYSTEINE-RICH ISOFORM OF NEUREGULIN CONTROLS THE LEVEL OF EXPRESSION OF NEURONAL NICOTINIC RECEPTOR CHANNELS DURING SYNAPTOGENESIS

We report here that neuregulin (NRG) isoforms with a conserved cystein e-rich domain (CRD) in their N terminus regulate expression of nicotin ic acetylcholine receptors (nAChRs) at developing interneuronal synaps es and report the isolation of transmembrane NRG isoforms with this CR D within the N-terminal portion. CRD-NRG mRNA and immunoreactive prote in are detected early in developing presynaptic (visceral motor) neuro ns. The levels of expression of CRD-NRG peak prior to the formation of synapses with their postsynaptic partners, the ganglionic sympathetic neurons. Recombinant CRD-NRG mimics the effects of presynaptic input on target neurons. Functional deletion of CRD-NRG from presynaptic neu rons abolishes the upregulation of nAChR expression induced by input-d erived soluble material. Thus, CRD-NRG appears to be both a necessary and a sufficient signal for the control of neuronal nAChR expression d uring synaptogenesis.