Role of the scaffolding protein SLC9A3R1 in the vomeronasal organ - from protein interactions to the physiology of pheromone detection
Final Report Abstract
In most mammals, the main and accessory olfactory systems detect of a variety of (semio)chemicals, many of which mediate olfactory-driven social and sexual behaviors. In general, chemosensation depends on G protein-coupled receptors (ORs, TAARs, V1Rs, V2Rs, FPR-rs proteins) that operate at remarkably low stimulus concentrations, thus, indicating highly sensitive and efficient signaling pathways. We therefore hypothesized (i) that signaling cascade proteins are organized in microdomains to ensure optimal signal transduction, and (ii) that the assembly of these domains involves scaffolding proteins. In the SPP 1392 project proposal, we aimed to identify and investigate PDZ domain-containing proteins as putative molecular organizers of signal transduction in chemosensory neurons. Accordingly, a major goal of this research was to analyze the functional role of scaffolding proteins in shaping ultrasensitive and highly selective chemosensory responses. For example, SLC9A3R1, a prototypical scaffolding protein that contains two PDZ domains and a carboxy-terminal ezrin-binding domain, was among the candidate proteins we were interested in. While we initially planned to specifically focus on SLC9A3R1 and its role in the mouse vomeronasal organ, we extended our research during the course of the project to a variety of proteins with similar functions and we also investigated cluster formation of prominent signaling components both in the main and accessory olfactory systems. Together, our tandem project revealed several mechanisms of transduction cascade organization in peripheral chemosensory neurons.
Publications
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(2014) Coexpression of Anoctamins in cilia of olfactory sensory neurons. Chemical Senses 40: 73-87
Henkel B, Drose D, Ackels T, Oberland S, Spehr M, Neuhaus EM
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(2014) Scaffolding by MUPP1 regulates odorant-mediated signaling in olfactory sensory neurons. Journal of Cell Science 127: 2518-2527
Baumgart S, Jansen F, Bintig W, Kalbe B, Herrmann C, Klumpers F, Köster SD, Scholz P, Rasche S, Dooley R, Metzler-Nolte N, Spehr M, Hatt H, Neuhaus EM
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(2015) CD36 is involved in oleic acid detection by the murine olfactory system. Front. Cell. Neurosci. 9: 366
Oberland S, Ackels T, Gaab S, Pelz T, Spehr J, Spehr M, Neuhaus EM
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(2016) Elevated cytosolic Cl– concentrations in dendritic knobs of mouse vomeronasal sensory neurons. Chemical Senses 41: 669-676
Untiet V, Moeller LM, Ibarra-Soria X, Sánchez-Andrade G, Stricker M, Neuhaus EM, Logan DW, Gensch T, Spehr M
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(2016) NHERF1 in Vomeronasal Microvilli: A putative organizer of signaling microdomains. Chemical Senses 42: 25-35
Henkel B, Bintig W, Bhat S, Spehr M, Neuhaus EM
