The cell biology of smell

DeMaria, Shannon; Ngai, John

doi:10.1083/jcb.201008163

Cited by 141 publications

(167 citation statements)

References 75 publications

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…1 These sensory neurons have axons that travel as the olfactory nerve (cranial nerve I) to terminate in the olfactory bulb. In turn, the olfactory bulb projects more centrally and contributes inputs for higher cortical processing, which results in olfactory perception.…”

mentioning

confidence: 99%

Olfactory assessment using the NIH Toolbox

et al. 2013

View full text Add to dashboard Cite

The human olfactory system provides us with information about our environment that is critical to our physical and psychological well-being. Individuals can vary widely in their ability to detect, recognize, and identify odors, but still be within the range of normal function. Although several standardized tests of odor identification are available, few specifically address the issues in testing very young children, most of whom are likely to be unfamiliar with many of the odor stimuli used in adult tests and have limited ability to read and identify labels to select among choices. Based on the format of the San Diego Odor Identification Test and the delivery system of the University of Pennsylvania Smell Identification Test, we developed 2 versions of an odor identification test using standardized odor stimuli in a scratch-and-sniff format in which participants match 5 (children) or 9 (adults) odors to pictures representing the odor source. Results from normative testing and validation showed that for most participants, the test could be completed in 5 minutes or less and that the poorer performance among the youngest children and the elderly was consistent with data from tests with larger numbers of items. Expanding on the pediatric version of the test with adult-specific and public health-relevant odors increased the ecological validity of the test and facilitated comparisons of intraindividual performance across developmental stages. The human olfactory system allows us to detect odors, to recognize and discriminate odor qualities, and to identify the sources of odors in our world. Humans are capable of detecting and discriminating thousands of different odorant molecules, many at extremely low concentrations (i.e., parts per billion or trillion). Our sense of smell provides us with information about our air, water, and food that is critical to our health and safety, nutrition, and psychological well-being.The process of olfaction is initiated when volatile chemicals stimulate olfactory receptor neurons located on a relatively small patch of specialized epithelial tissue high in the nasal cavity. 1 These sensory neurons have axons that travel as the olfactory nerve (cranial nerve I) to terminate in the olfactory bulb. In turn, the olfactory bulb projects more centrally and contributes inputs for higher cortical processing, which results in olfactory perception. 2 Odorants reach the olfactory receptors in 2 ways: they can enter the nostrils during normal inhalation (orthonasal route) or travel from the back of the oral cavity to the olfactory receptors via the nasal pharynx (retronasal route). The perception of food flavor involves a combination of olfactory activation caused by odorous compounds released into the nasopharynx retronasally through chewing, drinking, and deglutition, and the blending of taste (salty, sour, bitter, sweet, umami) and oral somatosensory sensations (texture, heat, cold). 3 Nasal blockage and swelling can prevent odors from entering the retronasal stream, resulting in a shi...

show abstract

mentioning

confidence: 99%

Olfactory assessment using the NIH Toolbox

et al. 2013

View full text Add to dashboard Cite

show abstract

“…G protein-coupled receptors (GPCRs) comprise a large family of transmembrane signaling proteins that directly bind and transduce a range of cues including photons, odorants, neurotransmitters, and peptides (Pierce et al 2002;Kato and Touhara 2009;Demaria and Ngai 2010;Sung and Chuang 2010;Chamero et al 2012;Frooninckx et al 2012;Montell 2012;Bathgate et al 2013). Regulation of GPCR function, including regulation of membrane targeting and trafficking to specific subcellular regions, is a major contributor to the tuning of signaling efficacy and fidelity (e.g., Deretic et al 1995; type, closely related members of a GPCR family can be differentially targeted to different cell compartment membranes.…”

mentioning

confidence: 99%

Diverse Cell Type-Specific Mechanisms Localize G Protein-Coupled Receptors to Caenorhabditis elegans Sensory Cilia

Brear

Yoon

Wojtyniak³

et al. 2014

Genetics

View full text Add to dashboard Cite

The localization of signaling molecules such as G protein-coupled receptors (GPCRs) to primary cilia is essential for correct signal transduction. Detailed studies over the past decade have begun to elucidate the diverse sequences and trafficking mechanisms that sort and transport GPCRs to the ciliary compartment. However, a systematic analysis of the pathways required for ciliary targeting of multiple GPCRs in different cell types in vivo has not been reported. Here we describe the sequences and proteins required to localize GPCRs to the cilia of the AWB and ASK sensory neuron types in Caenorhabditis elegans. We find that GPCRs expressed in AWB or ASK utilize conserved and novel sequences for ciliary localization, and that the requirement for a ciliary targeting sequence in a given GPCR is different in different neuron types. Consistent with the presence of multiple ciliary targeting sequences, we identify diverse proteins required for ciliary localization of individual GPCRs in AWB and ASK. In particular, we show that the TUB-1 Tubby protein is required for ciliary localization of a subset of GPCRs, implying that defects in GPCR localization may be causal to the metabolic phenotypes of tub-1 mutants. Together, our results describe a remarkable complexity of mechanisms that act in a protein-and cellspecific manner to localize GPCRs to cilia, and suggest that this diversity allows for precise regulation of GPCR-mediated signaling as a function of external and internal context. SIGNALING molecules must be precisely localized to specific subcellular domains to optimize detection and transduction of external stimuli. G protein-coupled receptors (GPCRs) comprise a large family of transmembrane signaling proteins that directly bind and transduce a range of cues including photons, odorants, neurotransmitters, and peptides (Pierce et al. 2002;Kato and Touhara 2009;Demaria and Ngai 2010;Sung and Chuang 2010;Chamero et al. 2012;Frooninckx et al. 2012;Montell 2012;Bathgate et al. 2013). Regulation of GPCR function, including regulation of membrane targeting and trafficking to specific subcellular regions, is a major contributor to the tuning of signaling efficacy and fidelity (e.g., Deretic et al. 1995;Ango et al. 2000;Xia et al. 2003;Esseltine et al. 2012;. However, much remains to be understood regarding the mechanisms by which GPCR trafficking and membrane localization are regulated.GPCR-mediated signal transduction in many cellular contexts requires these proteins to be localized to specialized microtubule-based primary cilia. For example, in photoreceptors and olfactory neurons, efficient sensory signal transduction is mediated via localization of rhodopsin and olfactory receptors, together with other signaling molecules, to photoreceptor outer segments and olfactory neuron cilia, respectively (Insinna and Besharse 2008;Berbari et al. 2009;Pifferi et al. 2010;Deretic and Wang 2012). Receptors in the Hedgehog (Hh) morphogen signaling pathway such as the Smoothened and Patched transmembrane proteins, and the G...

show abstract

“…insights into the pathogenesis of neurological disorders, results from our studies revealed that expression of select ORs in PBMC may serve as clinically assessable surrogate biological indices of TBI. ORs are G protein-coupled receptors known to be expressed in nasal epithelium olfactory neurons, where they are responsible for the detection of odorants [32]. However, ectopic expression of select ORs, defined as a biological event or process that occurs in an abnormal location or position in the brain or other tissues, has also been described [33].…”

Section: Discussionmentioning

confidence: 99%

Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimer's Disease

Pasinetti¹

2013

View full text Add to dashboard Cite

Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATEOct PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERIcahn School of Medicine at Mount Sinai 1 Gustave L. Levy Place New York, NY 10029 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTTraumatic Brain Injury (TBI) is a risk factor for subsequent development of Alzheimer's disease (AD). Abnormal tau processing is a common pathological feature of TBI and AD and tau neuropathology plays a key role in both TBI complications and AD dementia. This study is based on our recent findings of aberrant down-regulation of specific olfactory receptors (OR) as biological indices for TBI and down-regulation of OR TBI biomarkers following TBI might contribute to TBI-related tau neuropathology. We propose that down-regulation of select OR TBI biomarkers in the brain may contribute to the elevation of tau neuropathological phenotypes, thereby promoting the development of AD dementia among Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans with exposure to TBI. In Year 1, we found that activation of OR4M1 by a low affinity ligand resulted in reduced tau phosphorylation via JNK signaling pathway and a manuscript was published based on this finding. We constructed a virtual 3D structure model for OR4M1 to screen high affinity ligands. Fifty Seven (57) compounds were identified and clustered into 32 clusters based on their structure similarities. We found significant decrease of the blood OR contents in a rat model of TBI. Outcomes from our study will provide a better understanding of TBI complications and how it is related to AD. (Zhao et al., 2013). In addition, we found down-regulation of these ORs is significantly correlated with the severity of brain injury and TBI-specific symptoms, and a two-biomarker panel, comprised of OR11H1 and OR4M1, provides the best criterion for segregating the ...

show abstract

The cell biology of smell

Cited by 141 publications

References 75 publications

Olfactory assessment using the NIH Toolbox

Olfactory assessment using the NIH Toolbox

Diverse Cell Type-Specific Mechanisms Localize G Protein-Coupled Receptors to Caenorhabditis elegans Sensory Cilia

Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimer's Disease

Contact Info

Product

Resources

About