Article

Presynaptic Type III Neuregulin1-ErbB signaling targets α7 nicotinic acetylcholine receptors to axons

Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, New York, NY 10032, USA.
The Journal of Cell Biology (Impact Factor: 9.69). 06/2008; 181(3):511-21. DOI: 10.1083/jcb.200710037
Source: PubMed

ABSTRACT Type III Neuregulin1 (Nrg1) isoforms are membrane-tethered proteins capable of participating in bidirectional juxtacrine signaling. Neuronal nicotinic acetylcholine receptors (nAChRs), which can modulate the release of a rich array of neurotransmitters, are differentially targeted to presynaptic sites. We demonstrate that Type III Nrg1 back signaling regulates the surface expression of alpha7 nAChRs along axons of sensory neurons. Stimulation of Type III Nrg1 back signaling induces an increase in axonal surface alpha7 nAChRs, which results from a redistribution of preexisting intracellular pools of alpha7 rather than from increased protein synthesis. We also demonstrate that Type III Nrg1 back signaling activates a phosphatidylinositol 3-kinase signaling pathway and that activation of this pathway is required for the insertion of preexisting alpha7 nAChRs into the axonal plasma membrane. These findings, in conjunction with prior results establishing that Type III Nrg1 back signaling controls gene transcription, demonstrate that Type III Nrg1 back signaling can regulate both short-and long-term changes in neuronal function.

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    • "Type III Nrg1 is distinct from the other two types of Nrg1 and contains an extra N-terminal transmembrane structure. In type III Nrg1, initial proteolysis frees the EGF-like domain from the membrane and leads to juxtacrine signaling characterized by reciprocal intercellular communication (Bao et al. 2003; Hancock et al. 2008). Further cleavage releases a shorter peptide containing the EGF-like domain that functions in autocrine/paracrine interactions. "
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