EphB receptors co-distribute with a nicotinic receptor subtype and regulate nicotinic downstream signaling in neurons.
Activation of nicotinic acetylcholine receptors (nAChRs) on neurons engages calcium-dependent signaling pathways regulating numerous events. Receptors containing alpha7 subunits (alpha7-nAChRs) are prominent in this because of their abundance and high relative calcium permeability. We show here that EphB2 receptors are co-localized with postsynaptic alpha7-nAChRs on chick ciliary ganglion neurons and that treatment of the cells with an ephrinB1 construct to activate the EphB receptors exerts physical restraints on both classes of receptors, diminishing their dispersal after spine retraction or lipid raft disruption. Moreover, the ephrinB1/EphB receptor complex specifically enhances the ability of alpha7-nAChRs to activate the transcription factor CREB, acting through a pathway including a receptor tyrosine kinase, a Src family member, PI3 kinase, and protein kinase A most distally. The enhancement does not appear to result from a change in the alpha7-nAChR current amplitude, suggesting a downstream target. The results demonstrate a role for ephrin/EphB action in nicotinic signaling.
Liu
Zhaoping
Z
Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0357, USA.
Conroy
William G
WG
Stawicki
Tamara M
TM
Nai
Qiang
Q
Neff
Robert A
RA
Berg
Darwin K
DK
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D018678:Cholinergic Agents / Q000494:pharmacology; D036387:Ephrin-B1 / Q000378:metabolism; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D036081:Receptors, Eph Family / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D018678:Cholinergic Agents; D036387:Ephrin-B1; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D036081:Receptors, Eph Family; D002118:Calcium