Ca2+-activated Cl− currents in the murine vomeronasal organ enhance neuronal spiking but are dispensable for male–male aggression

Münch, Jonas; Billig, Gwendolyn; Hübner, Christian A.; Leinders‐Zufall, Trese; Zufall, Frank; Jentsch, Thomas J.

doi:10.1074/jbc.ra118.003153

Cited by 13 publications

(20 citation statements)

References 64 publications

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“…Specifically, conditional knockout of TMEM16A/ANO1 abolished the Ca 2+ -activated Cl − currents in mature VSNs, establishing ANO1 as the primary mediator of this transduction current ( Amjad et al 2015 ). This finding was recently confirmed in VSN recordings from ANO1/2 conditional double knockout mice, which show diminished spontaneous and pheromone-evoked action potential firing ( Münch et al 2018 ). It therefore came as a surprise that these double knockout mice did not display profound changes in resident–intruder paradigm-induced male territorial aggression ( Münch et al 2018 ).…”

Section: Vsn Transductionmentioning

confidence: 55%

“…This finding was recently confirmed in VSN recordings from ANO1/2 conditional double knockout mice, which show diminished spontaneous and pheromone-evoked action potential firing ( Münch et al 2018 ). It therefore came as a surprise that these double knockout mice did not display profound changes in resident–intruder paradigm-induced male territorial aggression ( Münch et al 2018 ).…”

Section: Vsn Transductionmentioning

confidence: 55%

“…Both routes, however, could mediate VSN adaptation and gain control by Ca 2+ /calmodulin-dependent inhibition of TRPC2 ( Spehr et al 2009 ; Figures 2 and 3 ), a mechanism that displays striking similarities to CNG channel modulation in canonical olfactory sensory neurons ( Bradley et al 2004 ). Another property shared with olfactory sensory neurons is Ca 2+ -dependent signal amplification via the ANO1 channel ( Yang and Delay 2010 ; Kim et al 2011 ; Dibattista et al 2012 ; Amjad et al 2015 ; Münch et al 2018 ). Moreover, a nonselective Ca 2+ -activated cation current ( I CAN ) has been identified in both hamster ( Liman 2003 ) and mouse ( Spehr et al 2009 ) VSNs.…”

Section: Vsn Transductionmentioning

confidence: 99%

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Signal Detection and Coding in the Accessory Olfactory System

et al. 2018

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In many mammalian species, the accessory olfactory system plays a central role in guiding behavioral and physiological responses to social and reproductive interactions. Because of its relatively compact structure and its direct access to amygdalar and hypothalamic nuclei, the accessory olfactory pathway provides an ideal system to study sensory control of complex mammalian behavior. During the last several years, many studies employing molecular, behavioral, and physiological approaches have significantly expanded and enhanced our understanding of this system. The purpose of the current review is to integrate older and newer studies to present an updated and comprehensive picture of vomeronasal signaling and coding with an emphasis on early accessory olfactory system processing stages. These include vomeronasal sensory neurons in the vomeronasal organ, and the circuitry of the accessory olfactory bulb. Because the overwhelming majority of studies on accessory olfactory system function employ rodents, this review is largely focused on this phylogenetic order, and on mice in particular. Taken together, the emerging view from both older literature and more recent studies is that the molecular, cellular, and circuit properties of chemosensory signaling along the accessory olfactory pathway are in many ways unique. Yet, it has also become evident that, like the main olfactory system, the accessory olfactory system also has the capacity for adaptive learning, experience, and state-dependent plasticity. In addition to describing what is currently known about accessory olfactory system function and physiology, we highlight what we believe are important gaps in our knowledge, which thus define exciting directions for future investigation.

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Section: Vsn Transductionmentioning

confidence: 55%

Section: Vsn Transductionmentioning

confidence: 55%

Section: Vsn Transductionmentioning

confidence: 99%

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Signal Detection and Coding in the Accessory Olfactory System

et al. 2018

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“…While OBPs binding to odors is well-documented at the biochemical level, very few investigations into OR binding have been reported. Activation of ORs with odorant molecules alone, with OBP bound or unbound to odorants, have been measured by electrophysiology [e.g., (4)] or other indirect techniques [e.g., (5, 6)]. This lack of direct evidence explains why the nature of ORs ligands is still uncertain.…”

Section: Introductionmentioning

confidence: 99%

Binding Specificity of Native Odorant-Binding Protein Isoforms Is Driven by Phosphorylation and O-N-Acetylglucosaminylation in the Pig Sus scrofa

et al. 2019

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Odorant-binding proteins (OBP) are secreted in the nasal mucus at the vicinity of olfactory receptors (ORs). They act, at least, as an interface between hydrophobic and volatile odorant molecules and the hydrophilic medium bathing the ORs. They have also been hypothesized to be part of the molecular coding of odors and pheromones, by forming specific complexes with odorant molecules that could ultimately stimulate ORs to trigger the olfactory transduction cascade. In a previous study, we have evidenced that pig olfactory secretome was composed of numerous olfactory binding protein isoforms, generated by O-GlcNAcylation and phosphorylation. In addition, we have shown that recombinant OBP (stricto sensu) produced in yeast is made up of a mixture of isoforms that differ in their phosphorylation pattern, which in turn determines binding specificity. Taking advantage of the high amount of OBP secreted by a single animal, we performed a similar study, under exactly the same experimental conditions, on native isoforms isolated from pig, Sus scrofa, nasal tissue. Four fractions were obtained by using strong anion exchange HPLC. Mapping of phosphorylation and O-GlcNAcylation sites by CID-nanoLC-MS/MS allowed unambiguous localization of phosphosites at S13 and T122 and HexNAc sites at S13 and S19. T112 or T115 could also be phosphorylated. BEMAD analysis suggested extra phosphosites located at S23, S24, S41, S49, S57, S67, and T71. Due to the very low stoichiometry of GlcNAc-peptides and phosphopeptides, these sites were identified on total mixture of OBP isoforms instead of HPLC-purified OBP isoforms. Nevertheless, binding properties of native OBP isoforms to specific ligands in S. scrofa were monitored by fluorescence spectroscopy. Recombinant phosphorylated OBP-Pichia isoforms bind steroids and fatty acids with slight differences. Native isoforms, that are phosphorylated but also O-GlcNAcylated show radically different binding affinities for the same compounds, which strongly suggests that O-GlcNAcylation increases the binding specificity of OBP isoforms. These findings extend the role of O-GlcNAc in regulating the function of proteins involved in many mechanisms of metabolic homeostasis, including extracellular signaling in olfaction. Data is available via ProteomeXChange with identifier PXD011371.

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“…4 c). Interruption of the signaling pathways can severely dampen animals’ behavioral responses, including food seeking, sex identification and preference, and aggression 21 , 22 . Previous studies have shown that abolishment of either Gαi2, Gαo or Gγ8 expression in the VNO abrogated the male–male aggression 17 , 23 , 24 .…”

Section: Discussionmentioning

confidence: 99%

G protein γ subunit Gγ13 is essential for olfactory function and aggressive behavior in mice

Chen

et al. 2018

NeuroReport

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Most olfactory receptors in vertebrates are G protein-coupled receptors, whose activation by odorants initiates intracellular signaling cascades through heterotrimeric G proteins consisting of α, β, and γ subunits. Abolishment of the α subunits such as Gαolf in the main olfactory epithelium and Gαi2 and Gαo in the vomeronasal organ resulted in anosmia and/or impaired behavioral responses. In this study, we report that a G protein γ subunit, Gγ13, is expressed in a spatiotemporal manner similar to those of Gαolf and Gαi2 in the olfactory system and vomeronasal organ, respectively. In addition, Gγ13 was found in the glomeruli of the main olfactory bulb but was largely absent in the glomeruli of the accessory olfactory bulb. Using the Cre-loxP system, the Gγ13’s gene Gng13 was nullified in the mature olfactory sensory neurons and apical vomeronasal sensory neurons where the Cre recombinase was expressed under the promoter of the Omp gene for the olfactory marker protein. Immunohistochemistry indicated much reduced expression of Gγ13 in the apical vomeronasal epithelium of the mutant mice. Behavioral experiments showed that the frequency and duration of aggressive encounters in the male mutant mice were significantly lower than in WT male mice. Taken together, these data suggest that the Gγ13 subunit is a critical signaling component in both the main olfactory epithelium and apical vomeronasal epithelium, and it plays an essential role in odor-triggered social behaviors including male–male aggression.

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Ca2+-activated Cl− currents in the murine vomeronasal organ enhance neuronal spiking but are dispensable for male–male aggression

Cited by 13 publications

References 64 publications

Signal Detection and Coding in the Accessory Olfactory System

Signal Detection and Coding in the Accessory Olfactory System

Binding Specificity of Native Odorant-Binding Protein Isoforms Is Driven by Phosphorylation and O-N-Acetylglucosaminylation in the Pig Sus scrofa

G protein γ subunit Gγ13 is essential for olfactory function and aggressive behavior in mice

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