β-Arrestin2-Mediated Internalization of Mammalian Odorant Receptors

Mashukova, Anastasia; Spehr, Marc; Hatt, Hanns; Neuhaus, Eva M.

doi:10.1523/jneurosci.2897-06.2006

Cited by 96 publications

(82 citation statements)

References 52 publications

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“…The phosphorylation of GPCR is followed by the recruitment of b-arrestins and internalization of GPCRs. A recent study has shown that olfactory receptors can also be inactivated by this mechanism (Mashukova et al 2006).…”

Section: Resultsmentioning

confidence: 99%

GPC-1, a G Protein γ-Subunit, Regulates Olfactory Adaptation in Caenorhabditis elegans

et al. 2009

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Caenorhabditis elegans genome carries two Gg genes, gpc-1 and gpc-2, and two Gb genes, gpb-1 and gpb-2. Of these, gpc-2 and gpb-1 are expressed ubiquitously and are essential for viability. Through a genetic screen, we identified gpc-1 as essential for olfactory adaptation. While wild-type animals show decreased chemotaxis to the odorant benzaldehyde after a short preexposure to the odorant, gpc-1 mutants are still attracted to the odorant after the same preexposure. Cell-specific rescue experiments show that gpc-1 acts in the AWC olfactory neurons. Coexpression of GPC-1 and GPB-1, but not GPB-2, caused enhanced adaptation, indicating that GPC-1 may act with GPB-1. On the other hand, knock down of gpc-2 by celltargeted RNAi caused reduced chemotaxis to the odorant in unadapted animals, indicating that GPC-2 mainly act for olfactory sensation and the two Gg's have differential functions. Nonetheless, overexpression of gpc-2 in AWC neurons rescued the adaptation defects of gpc-1 mutants, suggesting partially overlapping functions of the two Gg's. We further tested genetic interaction of gpc-1 with several other genes involved in olfactory adaptation. Our analyses place goa-1 Goa and let-60 Ras in parallel to gpc-1. In contrast, a gain-of-function mutation in egl-30 Gqa was epistatic to gpc-1, suggesting the possibility that gpc-1 Gg may act upstream of egl-30 Gqa.

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Section: Resultsmentioning

confidence: 99%

GPC-1, a G Protein γ-Subunit, Regulates Olfactory Adaptation in Caenorhabditis elegans

et al. 2009

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“…In mice, it has been shown that odorant receptors are internalized via clathrin-dependent endocytosis (Mashukova et al, 2006). The authors of that study also showed that prolonged odorant exposure led to the accumulation of receptors in recycling endosomes, and not to lysosomal degradation.…”

Section: Endocytosismentioning

confidence: 96%

“…Like other G-proteincoupled receptors (GPCRs) (Ferguson, 2001;Seachrist and Ferguson, 2003;von Zastrow, 2001), odorant receptors appear to be internalized upon activation via a clathrin-dependent process, as indicated by studies in channel catfish (Rankin et al, 1999) and mouse (Mashukova et al, 2006). After prolonged odorant exposure, receptors are not targeted to lysosomal degradation but accumulate in recycling endosomes, and adaptation of olfactory receptor neurons to odorants can be abolished by the inhibition of clathrin-mediated endocytosis (Mashukova et al, 2006). It is not clear to what extent the endocytosis observed in these experiments may be ligand specific.…”

Section: Introductionmentioning

confidence: 99%

Visualizing a set of olfactory sensory neurons responding to a bile salt

Døving

Hansson

Bäckström

et al. 2011

Journal of Experimental Biology

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SUMMARYIn the present study, we exposed the olfactory epithelia of crucian carp, Carassius carassius, and brown trout, Salmo trutta, to dextran coupled with Alexa dyes together with odorants. Dye uptake was severely reduced after pre-exposure to nocodazole, an inhibitor of microtubule polymerization that impairs endocytosis, supporting the hypothesis that odour-activated olfactory receptor molecules undergo endocytosis. Application of the bile acid taurolithocholate, a potent and specific odorant for fish, resulted in the labelling of a sparse (less than 3%) cell population with the typical morphology of ciliated sensory neurons (CSNs) -long dendrites and cell somata deep in the sensory epithelium. The dye was distributed throughout the sensory neuron, also revealing axons and target glomeruli. Stained axons redistribute at the entrance of the olfactory bulb and terminate in two small target areas, a dorsal and a medial one. These results are consistent with the notion that taurolithocholate is detected specifically by a few ciliated sensory neurons. Application of the olfactory epithelium of brown trout to bile acid stained cells with the appearance of CSNs. Application of an alarm agonist, hypxanthine-3-N-oxide, to crucian carp olfactory organ caused staining of another set of sensory neurons. Furthermore, our results show that odour-induced uptake of a dye can serve to identify the subtype of olfactory sensory neurons responding to a particular odorant, and to pinpoint the target regions of these neurons in the olfactory bulb as a first step to elucidating the neuronal network responding to a particular odour.

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“…In addition to 62 ORs, we also identified factors enhancing OR expression at the surface (REEP1, RPT1, and RTP2) (77,78) and different subunits of PKA attenuating OR activity by phosphorylation (79).…”

Section: Toward the Delineation Of The Ciliary Membrane Proteomementioning

confidence: 99%

The Membrane Proteome of Sensory Cilia to the Depth of Olfactory Receptors

Kuhlmann

Tschapek

Wiese

et al. 2014

Molecular & Cellular Proteomics

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In the nasal cavity, the nonmotile cilium of olfactory sensory neurons (OSNs) constitutes the chemosensory interface between the ambient environment and the brain. The unique sensory organelle facilitates odor detection for which it includes all necessary components of initial and downstream olfactory signal transduction. In addition to its function in olfaction, a more universal role in modulating different signaling pathways is implicated, for example, in neurogenesis, apoptosis, and neural regeneration. To further extend our knowledge about this multifunctional signaling organelle, it is of high importance to establish a most detailed proteome map of the ciliary membrane compartment down to the level of transmembrane receptors. We detached cilia from mouse olfactory epithelia via Ca 2؉ /K ؉ shock followed by the enrichment of ciliary membrane proteins at alkaline pH, and we identified a total of 4,403 proteins by gel-based and gel-free methods in conjunction with high resolution LC/MS. This study is the first to report the detection of 62 native olfactory receptor proteins and to provide evidence for their heterogeneous expression at the protein level. Quantitative data evaluation revealed four ciliary membrane-associated candidate proteins (the annexins ANXA1, ANXA2, ANXA5, and S100A5) with a suggested function in the regulation of olfactory signal transduction, and their presence in ciliary structures was confirmed by immunohistochemistry. Moreover, we corroborated the ciliary localization of the potassium-dependent Na ؉ /Ca 2؉ exchanger (NCKX) 4 and the plasma membrane Ca 2؉ -ATPase 1 (PMCA1) involved in olfactory signal termination, and we detected for the first time NCKX2 in olfactory cilia. Through comparison with transcriptome data specific for mature, ciliated OSNs, we finally delineated the membrane ciliome of OSNs. The membrane proteome of olfactory cilia established here is the most complete today, thus allowing us to pave new avenues for the study of diverse molecular functions and signaling pathways in and out of olfactory cilia and thus to advance our understanding of the biology of sensory organelles in general. Molecular & Cellular Proteomics 13:

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β-Arrestin2-Mediated Internalization of Mammalian Odorant Receptors

Cited by 96 publications

References 52 publications

GPC-1, a G Protein γ-Subunit, Regulates Olfactory Adaptation in Caenorhabditis elegans

GPC-1, a G Protein γ-Subunit, Regulates Olfactory Adaptation in Caenorhabditis elegans

Visualizing a set of olfactory sensory neurons responding to a bile salt

The Membrane Proteome of Sensory Cilia to the Depth of Olfactory Receptors

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