Identification of Thermosensory and Olfactory Neuron-Specific Genes via Expression Profiling of Single Neuron Types

Colosimo, Marc E.; Brown, Adam R.; Mukhopadhyay, Sutapa; Gabel, Christopher V.; Lanjuin, Anne; Samuel, Aravinthan D. T.; Sengupta, Piali

doi:10.1016/j.cub.2004.12.030

Cited by 119 publications

(98 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We and others previously showed that the AWB neurons express a subset of predicted GPCRs encoded by the C. elegans genome (Troemel et al 1995;Colosimo et al 2004;Nokes et al 2009;C. Bargmann, personal communication;www.…”

Section: Resultsmentioning

confidence: 99%

“…wormbase.org). Of these, str-1 and str-44 are expressed exclusively or primarily in AWB, whereas srsx-3, srd-23, sru-38, srab-16, and str-163 are expressed in AWB as well as in additional chemosensory neurons (Troemel et al 1995;Colosimo et al 2004;Nokes et al 2009;C. Bargmann, personal communication;www.wormbase.org).…”

Section: Resultsmentioning

confidence: 99%

“…Many of the amphid sensory neurons are multimodal; even within a modality such as chemosensation, each neuron responds to many chemicals (Bargmann and Horvitz 1991;Bargmann et al 1993;Hart et al 1995;Maricq et al 1995;Wes and Bargmann 2001;Biron et al 2008;Kuhara et al 2008;Ortiz et al 2009;Bretscher et al 2011). Reflecting this diversity of function, each sensory neuron expresses multiple putative sensory GPCRs from different subfamilies (Troemel et al 1995;Colosimo et al 2004;McCarroll et al 2005;Nokes et al 2009), providing an excellent system in which to begin to describe the diversity of mechanisms by which defined subsets of GPCRs are localized to cilia in individual cell types.Here we systematically characterize the cis-and transacting mechanisms required to localize GPCRs to the cilia of the AWB and ASK amphid chemosensory neuron types in C. elegans. We identify ciliary localized GPCRs in both neuron types and define conserved and new sequence motifs required for targeting these proteins to cilia.…”

mentioning

confidence: 99%

See 2 more Smart Citations

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

Brear

Yoon

Wojtyniak³

et al. 2014

Genetics

Self Cite

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

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

Brear

Yoon

Wojtyniak³

et al. 2014

Genetics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mutations in a DYF-5 homologue in Leishmania mexicana, LmxMPK9 (17), and in one of the two homologues in Chlamydomonas reinhardtii, LF4 (18), affect the length of the flagella of these organisms. In addition, several genome-wide approaches have identified DYF-5 and its homologues as likely ciliary proteins (21,(26)(27)(28)(29)(30).…”

mentioning

confidence: 99%

Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans

Burghoorn¹,

Dekkers²,

Rademakers³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

111

178

View full text Add to dashboard Cite

In the cilia of the nematode Caenorhabditis elegans, anterograde intraflagellar transport (IFT) is mediated by two kinesin-2 complexes, kinesin II and OSM-3 kinesin. These complexes function together in the cilia middle segments, whereas OSM-3 alone mediates transport in the distal segments. Not much is known about the mechanisms that compartmentalize the kinesin-2 complexes or how transport by both kinesins is coordinated. Here, we identify DYF-5, a conserved MAP kinase that plays a role in these processes. Fluorescence microscopy and EM revealed that the cilia of dyf-5 loss-of-function (lf) animals are elongated and are not properly aligned into the amphid channel. Some cilia do enter the amphid channel, but the distal ends of these cilia show accumulation of proteins. Consistent with these observations, we found that six IFT proteins accumulate in the cilia of dyf-5(lf) mutants. In addition, using genetic analyses and live imaging to measure the motility of IFT proteins, we show that dyf-5 is required to restrict kinesin II to the cilia middle segments. Finally, we show that, in dyf-5(lf) mutants, OSM-3 moves at a reduced speed and is not attached to IFT particles. We propose that DYF-5 plays a role in the undocking of kinesin II from IFT particles and in the docking of OSM-3 onto IFT particles.cilia length ͉ dyf-5 ͉ intraflagellar transport C ilia are present on almost every vertebrate cell and have important functions in motility or sensation. Within cilia, structural components and signaling molecules are transported by a specialized system, called intraflagellar transport (IFT) (1-5). Transport from the base of the cilia to the tip (anterograde) is mediated by kinesin-2 motor complexes, whereas dynein motor complexes mediate transport back to the base (retrograde). The nematode Caenorhabditis elegans has 60 ciliated neurons, including eight pairs of amphid neurons exposed to the environment (6). The cilia of these neurons can be divided into a middle segment with nine doublet microtubules and a distal segment with nine singlet microtubules (7). In the middle segments, two distinct kinesin-2 motor complexes mediate anterograde transport, heterotrimeric kinesin II, encoded by klp-11, klp-20, and kap-1 and homodimeric OSM-3 kinesin (8). In the distal segments, transport is mediated by only OSM-3 (8). Live imaging of the movement of these kinesins suggests that kinesin II alone moves at 0.5 m/s, and OSM-3 alone moves at 1.3 m/s, whereas the two motor complexes together move at 0.7 m/s (8). Recently, Pan et al. (9) have shown that these in vivo transport rates can be reconstituted in vitro by using purified kinesin II and OSM-3 motors. Thus far, two proteins have been identified that are required to stabilize IFT complexes transported by both kinesin II and OSM-3, BBS-7 and BBS-8 (10). However, it remains unclear how kinesin II is restricted to the cilia middle segments, whereas OSM-3 is allowed to enter the distal segments and what the functional significance is of this compartmentalization.Recently, Evans e...

show abstract

“…Our understanding of the molecular bases of sensation has benefited substantially from transcriptional analyses of photoreceptors (4), touch receptors (5), thermoreceptors (6), Merkel cells (7), and olfactory neurons (6,8). We have used a functionalgenomics approach to identify genes whose products are involved in the development, maintenance, and function of hair cells in the zebrafish.…”

mentioning

confidence: 99%

Analysis and functional evaluation of the hair-cell transcriptome

McDermott

Baucom

Hudspeth

2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

An understanding of the molecular bases of the morphogenesis, organization, and functioning of hair cells requires that the genes expressed in these cells be identified and their functions ascertained. After purifying zebrafish hair cells and detecting mRNAs with oligonucleotide microarrays, we developed a subtractive strategy that identified 1,037 hair cell-expressed genes whose cognate proteins subserve functions including membrane transport, synaptic transmission, transcriptional control, cellular adhesion and signal transduction, and cytoskeletal organization. To assess the validity of the subtracted hair-cell data set, we verified the presence of 11 transcripts in inner-ear tissue. Functional evaluation of two genes from the subtracted data set revealed their importance in hair bundles: zebrafish larvae bearing the seahorse and ift 172 mutations display specific kinociliary defects. Moreover, a search for candidate genes that underlie heritable deafness identified a human ortholog of a zebrafish hair-cell gene whose map location is bracketed by the markers of a deafness locus.auditory system ͉ balance ͉ hearing ͉ vestibular system ͉ zebrafish

show abstract

Identification of Thermosensory and Olfactory Neuron-Specific Genes via Expression Profiling of Single Neuron Types

Cited by 119 publications

References 31 publications

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

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

Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans

Analysis and functional evaluation of the hair-cell transcriptome

Contact Info

Product

Resources

About