Ca extrusion by NCX is compromised in olfactory sensory neurons of OMP mice.
BACKGROUND
The role of olfactory marker protein (OMP), a hallmark of mature olfactory sensory neurons (OSNs), has been poorly understood since its discovery. The electrophysiological and behavioral phenotypes of OMP knockout mice indicated that OMP influences olfactory signal transduction. However, the mechanism by which this occurs remained unknown.


RESULTS
We used intact olfactory epithelium obtained from WT and OMP(-/-) mice to monitor the Ca(2+) dynamics induced by the activation of cyclic nucleotide-gated channels, voltage-operated Ca(2+) channels, or Ca(2+) stores in single dendritic knobs of OSNs. Our data suggested that OMP could act to modulate the Ca(2+)-homeostasis in these neurons by influencing the activity of the plasma membrane Na(+)/Ca(2+)-exchanger (NCX). Immunohistochemistry verifies colocalization of NCX1 and OMP in the cilia and knobs of OSNs. To test the role of NCX activity, we compared the kinetics of Ca(2+) elevation by stimulating the reverse mode of NCX in both WT and OMP(-/-) mice. The resulting Ca(2+) responses indicate that OMP facilitates NCX activity and allows rapid Ca(2+) extrusion from OSN knobs. To address the mechanism by which OMP influences NCX activity in OSNs we studied protein-peptide interactions in real-time using surface plasmon resonance technology. We demonstrate the direct interaction of the XIP regulatory-peptide of NCX with calmodulin (CaM).


CONCLUSIONS
Since CaM also binds to the Bex protein, an interacting protein partner of OMP, these observations strongly suggest that OMP can influence CaM efficacy and thus alters NCX activity by a series of protein-protein interactions.
Kwon
Hyun J
HJ
Department of Anatomy and Neurobiology, School of Medicine, University of Maryland, Baltimore, Maryland, United States of America.
Koo
Jae Hyung
JH
Zufall
Frank
F
Leinders-Zufall
Trese
T
Margolis
Frank L
FL
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000235:genetics / Q000502:physiology*; D004594:Electrophysiology / Q000379:methods; D007700:Kinetics; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D051842:Olfactory Marker Protein / Q000235:genetics / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D010641:Phenotype; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000502:physiology*; D020349:Surface Plasmon Resonance
D002147:Calmodulin; C499849:NCX1 protein, mouse; D051842:Olfactory Marker Protein; D019831:Sodium-Calcium Exchanger; D002118:Calcium