Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons.
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.
Hancock
Melissa L
ML
Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, New York, NY 10032, USA.
Canetta
Sarah E
SE
Role
Lorna W
LW
Talmage
David A
DA
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D004705:Endocytosis / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D018739:Oncogene Proteins v-erbB / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579166:Chrna7 protein, mouse; D020890:Neuregulin-1; D018739:Oncogene Proteins v-erbB; D020033:Protein Isoforms; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt