Transmembrane protein OSTA-1 shapes sensory cilia morphology via regulation of intracellular membrane trafficking in <i>C. elegans</i>

Olivier-Mason, Anique; Wojtyniak, Martin; Bowie, Rachel V.; Nechipurenko, Inna V.; Blacque, Oliver E.; Sengupta, Piali

doi:10.1242/dev.086249

Cited by 27 publications

(16 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is in contrast to other transmembrane signaling molecules, such as GPCRs and TRPV channels, which appear to move throughout C. elegans cilia (Kaplan et al, 2012;Olivier-Mason et al, 2013;Qin et al, 2005). However, the Kinesin-II motor subunit appears to play a role in regulating correct TAX-2 and TAX-4 localization to the AWB cilia because in kap-1 mutants, we observed accumulation of these fusion proteins at the dendritic tip in a subset of cells.…”

Section: Discussioncontrasting

confidence: 63%

“…2B), exhibits markedly distinct cilia morphologies (Perkins et al, 1986;Ward et al, 1975), and requires different mechanisms of cilia biogenesis and ciliary protein transport (Kaplan et al, 2012;Mukhopadhyay et al, 2007;Olivier-Mason et al, 2013;Snow et al, 2004). For instance, whereas the heterotrimeric Kinesin-II and homodimeric OSM-3 anterograde motors function redundantly to build the middle segments of both AWB and ASK-like cilia, OSM-3 is required to generate the distal segments of only ASK-like cilia, not AWB cilia (Mukhopadhyay et al, 2007;Snow et al, 2004).…”

Section: Journal Of Cell Sciencementioning

confidence: 99%

“…For instance, whereas the heterotrimeric Kinesin-II and homodimeric OSM-3 anterograde motors function redundantly to build the middle segments of both AWB and ASK-like cilia, OSM-3 is required to generate the distal segments of only ASK-like cilia, not AWB cilia (Mukhopadhyay et al, 2007;Snow et al, 2004). In addition, mutations in proteins required for ciliary protein trafficking appear to affect ciliary transmembrane protein localization differently in AWB and ASK, or ASK-like cilia (Kaplan et al, 2012;Olivier-Mason et al, 2013).…”

Section: Journal Of Cell Sciencementioning

confidence: 99%

See 2 more Smart Citations

Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization inC. elegans

Wojtyniak

Brear

O'Halloran

et al. 2013

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

SummaryPrimary cilia are ubiquitous sensory organelles that concentrate transmembrane signaling proteins essential for sensing environmental cues. Mislocalization of crucial ciliary signaling proteins, such as the tetrameric cyclic nucleotide-gated (CNG) channels, can lead to cellular dysfunction and disease. Although several cis-and trans-acting factors required for ciliary protein trafficking and localization have been identified, whether these mechanisms act in a protein-and cell-specific manner is largely unknown. Here, we show that CNG channel subunits can be localized to discrete ciliary compartments in individual sensory neurons in C. elegans, suggesting that channel composition is heterogeneous across the cilium. We demonstrate that ciliary localization of CNG channel subunits is interdependent on different channel subunits in specific cells, and identify sequences required for efficient ciliary targeting and localization of the TAX-2 CNGB and TAX-4 CNGA subunits. Using a candidate gene approach, we show that Inversin, transition zone proteins, intraflagellar transport motors and a MYND-domain protein are required to traffic and/or localize CNG channel subunits in both a cell-and channel subunit-specific manner. We further find that TAX-2 and TAX-4 are relatively immobile in specific sensory cilia subcompartments, suggesting that these proteins undergo minimal turnover in these domains in mature cilia. Our results uncover unexpected diversity in the mechanisms that traffic and localize CNG channel subunits to cilia both within and across cell types, highlighting the essential contribution of this process to cellular functions.

show abstract

Section: Discussioncontrasting

confidence: 63%

Section: Journal Of Cell Sciencementioning

confidence: 99%

Section: Journal Of Cell Sciencementioning

confidence: 99%

See 1 more Smart Citation

Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization inC. elegans

Wojtyniak

Brear

O'Halloran

et al. 2013

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although fewer GPCRs expressed in ASK have been identified, this neuron type also expresses the srbc-64 and srbc-66 pheromone receptors (Kim et al 2009). Only STR-1, and the SRBC-64 and SRBC-66 pheromone receptors, have been shown to be localized to the sensory cilia of AWB and ASK, respectively Kim et al 2009;Olivier-Mason et al 2013). The characterized expression pattern of multiple receptors in these neuron types, together with our previous analyses showing distinct mechanisms of ciliary membrane protein localization in AWB and ASK , prompted us to analyze GPCR localization mechanisms in these two sensory neurons in detail.…”

Section: Resultsmentioning

confidence: 99%

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

“…The findings from these transcriptional studies will have to be integrated with other established mechanisms for generating ciliary diversity, such as variations in IFT (reviewed by Silverman and Leroux, 2009), translational control [e.g. by microRNAs (Marcet et al, 2011;Wang et al, 2013)], membrane trafficking (Olivier-Mason et al, 2013) and post-translational modifications of ciliary components, such as acetylation and glutamylation of tubulin (reviewed by Konno et al, 2012). Importantly, all of this information will have a profound impact on our understanding of how defects in the proper differentiation and function of cilia can cause such a wide and rapidly expanding spectrum of diseases in humans.…”

Section: Discussionmentioning

confidence: 99%

Switching on cilia: transcriptional networks regulating ciliogenesis

et al. 2014

View full text Add to dashboard Cite

Cilia play many essential roles in fluid transport and cellular locomotion, and as sensory hubs for a variety of signal transduction pathways. Despite having a conserved basic morphology, cilia vary extensively in their shapes and sizes, ultrastructural details, numbers per cell, motility patterns and sensory capabilities. Emerging evidence indicates that this diversity, which is intimately linked to the different functions that cilia perform, is in large part programmed at the transcriptional level. Here, we review our understanding of the transcriptional control of ciliary biogenesis, highlighting the activities of FOXJ1 and the RFX family of transcriptional regulators. In addition, we examine how a number of signaling pathways, and lineage and cell fate determinants can induce and modulate ciliogenic programs to bring about the differentiation of distinct cilia types.

show abstract

Transmembrane protein OSTA-1 shapes sensory cilia morphology via regulation of intracellular membrane trafficking in C. elegans

Cited by 27 publications

References 94 publications

Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization inC. elegans

Cell- and subunit-specific mechanisms of CNG channel ciliary trafficking and localization inC. elegans

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

Switching on cilia: transcriptional networks regulating ciliogenesis

Contact Info

Product

Resources

About