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C I Bargmann

Publications and source records attributed to C I Bargmann.

At least 19 recordsLinked to original sources
PubMed2002

Single ionic channels of two Caenorhabditis elegans chemosensory neurons in native membrane.

The genome of Caenorhabditis elegans contains representatives of the channel families found in both vertebrate and invertebrate nervous systems. However, it lacks the ubiquitous Hodgkin-Huxley Na+ channel that is integral to long-distance signaling in other animals. Nematode neurons are presumed to communicate by electrotonic conduction and graded depolarizations. This fundamental difference in operating principle may require different channel populations to regulate transmission and transmitter release. We have sampled ionic channels from the somata of two chemosensory neurons (AWA and AWC) of C. elegans. A Ca2+-activated, outwardly rectifying channel has a conductance of 67 pS and a reversal potential indicating selectivity for K+. An inwardly rectifying channel is active at potentials more negative than -50 mV. The inward channel is notably flickery even in the absence of divalent cations; this prevented determination of its conductance and reversal potential. Both of these channels were inactive over a range of membrane potentials near the likely cell resting potential; this would account for the region of very high membrane resistance observed in whole-cell recordings. A very-large-conductance (> 100 pS), inwardly rectifying channel may account for channel-like fluctuations seen in whole-cell recordings.

Animals↗
PubMed2001

C. elegans slit acts in midline, dorsal-ventral, and anterior-posterior guidance via the SAX-3/Robo receptor.

Robo receptors interact with ligands of the Slit family. The nematode C. elegans has one Robo receptor (SAX-3) and one Slit protein (SLT-1), which direct ventral axon guidance and guidance at the midline. In larvae, slt-1 expression in dorsal muscles repels axons to promote ventral guidance. SLT-1 acts through the SAX-3 receptor, in parallel with the ventral attractant UNC-6 (Netrin). Removing both UNC-6 and SLT-1 eliminates all ventral guidance information for some axons, revealing an underlying longitudinal guidance pathway. In the embryo, slt-1 is expressed at high levels in anterior epidermis. Embryonic expression of SLT-1 provides anterior-posterior guidance information to migrating CAN neurons. Surprisingly, slt-1 mutants do not exhibit the nerve ring and epithelial defects of sax-3 mutants, suggesting that SAX-3 has both Slit-dependent and Slit-independent functions in development.

Animals↗
PubMed2001

Sensory experience and sensory activity regulate chemosensory receptor gene expression in Caenorhabditis elegans.

Changes in the environment cause both short-term and long-term changes in an animal's behavior. Here we show that specific sensory experiences cause changes in chemosensory receptor gene expression that may alter sensory perception in the nematode Caenorhabditis elegans. Three predicted chemosensory receptor genes expressed in the ASI chemosensory neurons, srd-1, str-2, and str-3, are repressed by exposure to the dauer pheromone, a signal of crowding. Repression occurs at pheromone concentrations below those that induce formation of the alternative dauer larva stage, suggesting that exposure to pheromones can alter the chemosensory behaviors of non-dauer animals. In addition, ASI expression of srd-1, but not str-2 and str-3, is induced by sensory activity of the ASI neurons. Expression of two receptor genes is regulated by developmental entry into the dauer larva stage. srd-1 expression in ASI neurons is repressed in dauer larvae. str-2 expression in dauer animals is induced in the ASI neurons, but repressed in the AWC neurons. The ASI and AWC neurons remodel in the dauer stage, and these results suggest that their sensory specificity changes as well. We suggest that experience-dependent changes in chemosensory receptor gene expression may modify olfactory behaviors.

Animals↗
PubMed2001

Polarized dendritic transport and the AP-1 mu1 clathrin adaptor UNC-101 localize odorant receptors to olfactory cilia.

Odorant receptors and signaling proteins are localized to sensory cilia on olfactory dendrites. Using a GFP-tagged odorant receptor protein, Caenorhabditis elegans ODR-10, we characterized protein sorting and transport in olfactory neurons in vivo. ODR-10 is transported in rapidly moving dendritic vesicles that shuttle between the cell body and the cilia. Anterograde and retrograde vesicles move at different speeds, suggesting that dendrites have polarized transport mechanisms. Residues immediately after the seventh membrane-spanning domain of ODR-10 are required for localization; these residues are conserved in many G protein-coupled receptors. UNC-101 encodes a mu1 subunit of the AP-1 clathrin adaptor complex. In unc-101 mutants, dendritic vesicles are absent, ODR-10 receptor is evenly distributed over the plasma membrane, and other cilia membrane proteins are also mislocalized, implicating AP-1 in protein sorting to olfactory cilia.

Amino Acid Sequence↗
PubMed2001

The CaMKII UNC-43 activates the MAPKKK NSY-1 to execute a lateral signaling decision required for asymmetric olfactory neuron fates.

A stochastic cell fate decision mediated by axon contact and calcium signaling causes one of the two bilaterally symmetric AWC neurons, either AWCL or AWCR, to express the candidate olfactory receptor str-2. nsy-1 mutants express str-2 in both neurons, disrupting AWC asymmetry. nsy-1 encodes a homolog of the human MAP kinase kinase kinase (MAPKKK) ASK1, an activator of JNK and p38 kinases. Based on genetic epistasis analysis, nsy-1 appears to act downstream of the CaMKII unc-43, and NSY-1 associates with UNC-43, suggesting that UNC-43/CaMKII activates the NSY-1 MAP kinase cassette. Mosaic analysis demonstrates that UNC-43 and NSY-1 act primarily in a cell-autonomous execution step that represses str-2 expression in one AWC cell, downstream of the initial lateral signaling pathway that coordinates the fates of the two cells.

Amino Acid Sequence↗
PubMed2001

C. elegans odour discrimination requires asymmetric diversity in olfactory neurons.

Caenorhabditis elegans senses at least five attractive odours with a single pair of olfactory neurons, AWC, but can distinguish among these odours in behavioural assays. The two AWC neurons are structurally and functionally similar, but the G-protein-coupled receptor STR-2 is randomly expressed in either the left or the right AWC neuron, never in both. Here we describe the isolation of a mutant, ky542, with specific defects in odour discrimination and odour chemotaxis. ky542 is an allele of nsy-1, a neuronal symmetry, or Nsy, mutant in which STR-2 is expressed in both AWC neurons. Other Nsy mutants exhibit discrimination and olfactory defects like those of nsy-1 mutants. Laser ablation of the AWC neuron that does not express STR-2 (AWCOFF) recapitulates the behavioural phenotype of Nsy mutants, whereas laser ablation of the STR-2-expressing AWC neuron (AWCON) causes different chemotaxis defects. We propose that odour discrimination can be achieved by segregating the detection of different odours into distinct olfactory neurons or into unique combinations of olfactory neurons.

Animals↗
PubMed2001

The SAD-1 kinase regulates presynaptic vesicle clustering and axon termination.

During synapse formation, presynaptic axon outgrowth is terminated, presynaptic clusters of vesicles are associated with active zone proteins, and active zones are aligned with postsynaptic neurotransmitter receptors. We report here the identification of a novel serine/threonine kinase, SAD-1, that regulates several aspects of presynaptic differentiation in C. elegans. In sad-1 mutant animals presynaptic vesicle clusters in sensory neurons and motor neurons are diffuse and disorganized. Sensory axons fail to terminate in sad-1 mutants, whereas overexpression of SAD-1 causes sensory axons to terminate prematurely. SAD-1 protein is expressed in the nervous system and localizes to synapse-rich regions of the axons. SAD-1 is related to PAR-1, a kinase that regulates cell polarity during asymmetric cell division. Overexpression of SAD-1 causes mislocalization of vesicle proteins to dendrites, suggesting that sad-1 affects axonal-dendritic polarity as well as synaptic development.

Animals↗
PubMed2001

Ca2+ signaling via the neuronal calcium sensor-1 regulates associative learning and memory in C. elegans.

On a radial temperature gradient, C. elegans worms migrate, after conditioning with food, toward their cultivation temperature and move along this isotherm. This experience-dependent behavior is called isothermal tracking (IT). Here we show that the neuron-specific calcium sensor-1 (NCS-1) is essential for optimal IT. ncs-1 knockout animals show major defects in IT behavior, although their chemotactic, locomotor, and thermal avoidance behaviors are normal. The knockout phenotype can be rescued by reintroducing wild-type NCS-1 into the AIY interneuron, a key component of the thermotaxis network. A loss-of-function form of NCS-1 incapable of binding calcium does not restore IT, whereas NCS-1 overexpression enhances IT performance levels, accelerates learning (faster acquisition), and produces a memory with slower extinction. Thus, proper calcium signaling via NCS-1 defines a novel pathway essential for associative learning and memory.

Animals↗
PubMed2001

Dynamic regulation of axon guidance.

To reach their proper targets, axons rely upon the actions of highly conserved families of attractive and repulsive guidance molecules, including the netrins, Slits, semaphorins and ephrins. These guidance systems are used to generate an astonishingly varied set of neuronal circuits. Here we consider the mechanisms by which a few guidance systems can be used to generate diverse outcomes. Recent studies have revealed extensive transcriptional and post-transcriptional regulation of guidance cues and their receptors, as well as combinatorial mechanisms that integrate information from different families of guidance cues.

Animals↗
PubMed2001

The Caenorhabditis elegans odr-2 gene encodes a novel Ly-6-related protein required for olfaction.

Caenorhabditis elegans odr-2 mutants are defective in the ability to chemotax to odorants that are recognized by the two AWC olfactory neurons. Like many other olfactory mutants, they retain responses to high concentrations of AWC-sensed odors; we show here that these residual responses are caused by the ability of other olfactory neurons (the AWA neurons) to be recruited at high odor concentrations. odr-2 encodes a membrane-associated protein related to the Ly-6 superfamily of GPI-linked signaling proteins and is the founding member of a C. elegans gene family with at least seven other members. Alternative splicing of odr-2 yields three predicted proteins that differ only at the extreme amino terminus. The three isoforms have different promoters, and one isoform may have a unique role in olfaction. An epitope-tagged ODR-2 protein is expressed at high levels in sensory neurons, motor neurons, and interneurons and is enriched in axons. The AWC neurons are superficially normal in their development and structure in odr-2 mutants, but their function is impaired. Our results suggest that ODR-2 may regulate AWC signaling within the neuronal network required for chemotaxis.

Alternative Splicing↗
PubMed2001

Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis.

The Caenorhabditis elegans genome contains three rac-like genes, ced-10, mig-2, and rac-2. We report that ced-10, mig-2 and rac-2 act redundantly in axon pathfinding: inactivating one gene had little effect, but inactivating two or more genes perturbed both axon outgrowth and guidance. mig-2 and ced-10 also have redundant functions in some cell migrations. By contrast, ced-10 is uniquely required for cell-corpse phagocytosis, and mig-2 and rac-2 have only subtle roles in this process. Rac activators are also used differentially. The UNC-73 Trio Rac GTP exchange factor affected all Rac pathways in axon pathfinding and cell migration but did not affect cell-corpse phagocytosis. CED-5 DOCK180, which acts with CED-10 Rac in cell-corpse phagocytosis, acted with MIG-2 but not CED-10 in axon pathfinding. Thus, distinct regulatory proteins modulate Rac activation and function in different developmental processes.

Amino Acid Sequence↗
PubMed2000

Olfaction and odor discrimination are mediated by the C. elegans guanylyl cyclase ODR-1.

Animals in complex environments must discriminate between salient and uninformative sensory cues. Caenorhabditis elegans uses one pair of olfactory neurons called AWC to sense many different odorants, yet the animal can distinguish each odorant from the others in discrimination assays. We demonstrate that the transmembrane guanylyl cyclase ODR-1 is essential for responses to all AWC-sensed odorants. ODR-1 appears to be a shared signaling component downstream of odorant receptors. Overexpression of ODR-1 protein indicates that ODR-1 can influence odor discrimination and adaptation as well as olfaction. Adaptation to one odorant, butanone, is disrupted by ODR-1 overexpression. Olfactory discrimination is also disrupted by ODR-1 overexpression, probably by overproduction of the shared second messenger cGMP. We propose that AWC odorant signaling pathways are insulated to permit odor discrimination.

Adaptation, Physiological↗
PubMed2000

Neuronal cell shape and neurite initiation are regulated by the Ndr kinase SAX-1, a member of the Orb6/COT-1/warts serine/threonine kinase family.

The Caenorhabditis elegans sax-1 gene regulates several aspects of neuronal cell shape. sax-1 mutants have expanded cell bodies and ectopic neurites in many classes of neurons, suggesting that SAX-1 functions to restrict cell and neurite growth. The ectopic neurites in sensory neurons of sax-1 mutants resemble the defects caused by decreased sensory activity. However, the activity-dependent pathway, mediated in part by the UNC-43 calcium/calmodulin-dependent kinase II, functions in parallel with SAX-1 to suppress neurite initiation. sax-1 encodes a serine/threonine kinase in the Ndr family that is related to the Orb6 (Schizosaccharomyces pombe), Warts/Lats (Drosophila), and COT-1 (Neurospora) kinases that function in cell shape regulation. These kinases have similarity to Rho kinases but lack consensus Rho-binding domains. Dominant negative mutations in the C. elegans RhoA GTPase cause neuronal cell shape defects similar to those of sax-1 mutants, and genetic interactions between rhoA and sax-1 suggest shared functions. These results suggest that SAX-1/Ndr kinases are endogenous inhibitors of neurite initiation and cell spreading.

Amino Acid Sequence↗
PubMed1999

Lateral signaling mediated by axon contact and calcium entry regulates asymmetric odorant receptor expression in C. elegans.

C. elegans detects several odorants with the bilaterally symmetric pair of AWC olfactory neurons. A stochastic, coordinated decision ensures that the candidate odorant receptor gene str-2 is expressed in only one AWC neuron in each animal--either the left or the right neuron, but never both. An interaction between the two AWC neurons generates asymmetric str-2 expression in a process that requires normal axon guidance and probably AWC axon contact. This interaction induces str-2 expression by reducing calcium signaling through a voltage-dependent Ca2+ channel and the CaM kinase II UNC-43. CaMKII activity acts as a switch in the initial decision to express str-2; thus, calcium signals can define distinct cell types during neuronal development. A cGMP signaling pathway that is used in olfaction maintains str-2 expression after the initial decision has been made.

Animals↗
PubMed1999

Role of a class DHC1b dynein in retrograde transport of IFT motors and IFT raft particles along cilia, but not dendrites, in chemosensory neurons of living Caenorhabditis elegans.

The heterotrimeric motor protein, kinesin-II, and its presumptive cargo, can be observed moving anterogradely at 0.7 microm/s by intraflagellar transport (IFT) within sensory cilia of chemosensory neurons of living Caenorhabditis elegans, using a fluorescence microscope-based transport assay (Orozco, J.T., K.P. Wedaman, D. Signor, H. Brown, L. Rose, and J.M. Scholey. 1999. Nature. 398:674). Here, we report that kinesin-II, and two of its presumptive cargo molecules, OSM-1 and OSM-6, all move at approximately 1.1 microm/s in the retrograde direction along cilia and dendrites, which is consistent with the hypothesis that these proteins are retrieved from the distal endings of the cilia by a retrograde transport pathway that moves them along cilia and then dendrites, back to the neuronal cell body. To test the hypothesis that the minus end-directed microtubule motor protein, cytoplasmic dynein, drives this retrograde transport pathway, we visualized movement of kinesin-II and its cargo along dendrites and cilia in a che-3 cytoplasmic dynein mutant background, and observed an inhibition of retrograde transport in cilia but not in dendrites. In contrast, anterograde IFT proceeds normally in che-3 mutants. Thus, we propose that the class DHC1b cytoplasmic dynein, CHE-3, is specifically responsible for the retrograde transport of the anterograde motor, kinesin-II, and its cargo within sensory cilia, but not within dendrites.

Animals↗
PubMed1999

Alternative olfactory neuron fates are specified by the LIM homeobox gene lim-4.

The Caenorhabditis elegans AWA, AWB, and AWC olfactory neurons are each required for the recognition of a specific subset of volatile odorants. lim-4 mutants express an AWC reporter gene inappropriately in the AWB olfactory neurons and fail to express an AWB reporter gene. The AWB cells are morphologically transformed toward an AWC fate in lim-4 mutants, adopting cilia and axon morphologies characteristic of AWC. AWB function is also transformed in these mutants: Rather than mediating the repulsive behavioral responses appropriate for AWB, the AWB neurons mediate attractive responses, like AWC. LIM-4 is a predicted LIM homeobox gene that is expressed in AWB and a few other head neurons. Ectopic expression of LIM-4 in the AWC neuron pair is sufficient to force those cells to adopt an AWB fate. The AWA nuclear hormone receptor ODR-7 described previously also represses AWC genes, as well as inducing AWA genes. We propose that the LIM-4 and ODR-7 transcription factors function to diversify C. elegans olfactory neuron identities, driving them from an AWC-like state into alternative fates.

Amino Acid Sequence↗
PubMed1999

Functional reconstitution of a heteromeric cyclic nucleotide-gated channel of Caenorhabditis elegans in cultured cells.

The tax-4 and tax-2 genes of Caenorhabditis elegans are essential for normal olfaction, gustation, and thermosensation, suggesting that they have a role in sensory transduction. The predicted products of these genes are similar to the cyclic nucleotide-gated (CNG) channel subunits used in vertebrate vision and olfaction: TAX-4 is highly related to those alpha subunits, while TAX-2 is most closely related to the beta subunits of the rod phototransduction channels. TAX-4 has previously been shown to form a highly sensitive cGMP-gated channel when expressed in human HEK293 cells. Here we show that TAX-4 and TAX-2 form a heteromeric channel when expressed in HEK293 cells, but TAX-2 does not form a channel on its own. Since these genes are expressed in the same neurons, most of the native channels in C. elegans are likely to be hetero-oligomers of TAX-4 and TAX-2 subunits, with TAX-4 as the alpha subunit and TAX-2 acting as a modifying beta subunit. The heteromeric TAX-4/TAX-2 channel is 25-fold less sensitive to cGMP than the TAX-4 channel, but it remains highly selective for cGMP over cAMP. The heteromeric channel and the TAX-4 homomeric channel differ in their blockage by divalent cations and in their single channel properties. These results suggest that cGMP is used as the second messenger during sensory signal transduction in C. elegans, and that distinct roles for alpha and beta subunits of CNG channels are conserved in vertebrate and invertebrate signal transduction.

Animals↗