CaMKI-Dependent Regulation of Sensory Gene Expression Mediates Experience-Dependent Plasticity in the Operating Range of a Thermosensory Neuron

Yu, Yanxun V.; Bell, Harold W.; Glauser, Dominique A.; Hooser, Stephen D. Van; Goodman, Miriam B.; Sengupta, Piali

doi:10.1016/j.neuron.2014.10.046

Cited by 66 publications

(150 citation statements)

References 35 publications

(66 reference statements)

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“…Elevated Ca 2ϩ modulates thermotaxis by upregulating Ca 2ϩ /calmodulin-activated protein kinase 1 (CMK-1) or calcineurin (TAX-6), a protein phosphatase. CMK-1 induces gcy gene expression, whereas TAX-6 is required to sustain optimal TAX-2/TAX-4-mediated Ca 2ϩ uptake (59,60). Neither CMK-1 nor TAX-6 directly regulates NT or NP release from vesicles.…”

Section: Discussionmentioning

confidence: 99%

A Calcium- and Diacylglycerol-Stimulated Protein Kinase C (PKC), Caenorhabditis elegans PKC-2, Links Thermal Signals to Learned Behavior by Acting in Sensory Neurons and Intestinal Cells

Land

Rubin

2017

Molecular and Cellular Biology

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Ca 2ϩ -and diacylglycerol (DAG)-activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a Caenorhabditis elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (T c ) and migrates along the T c within a 17 to 25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2 Ϫ/Ϫ animals. Cell-specific manipulation of PKC-2 activity revealed that thermotaxis is controlled by cooperative PKC-2-mediated signaling in both AFD sensory neurons and intestinal cells. Cold-directed migration (cryophilic drive) precedes T c tracking during thermotaxis. Analysis of temperature-directed behaviors elicited by persistent PKC-2 activation or inhibition in AFD (or intestine) disclosed that PKC-2 regulates initiation and duration of cryophilic drive. In AFD neurons, PKC-2 is a Ca 2ϩ sensor and signal amplifier that operates downstream from cyclic GMP-gated cation channels and distal guanylate cyclases. UNC-18, which regulates neurotransmitter and neuropeptide release from synaptic vesicles, is a critical PKC-2 effector in AFD. UNC-18 variants, created by mutating Ser 311 or Ser 322 , disrupt thermotaxis and suppress PKC-2-dependent cryophilic migration.KEYWORDS C. elegans signal integration, MUNC18 and UNC-18, calcium, diacylglycerol-activated PKC, cyclic GMP-gated channel, protein kinase C, regulation of learned behavior, sensory neuron, signal transduction, thermotaxis D iacylglycerol (DAG) and free cytoplasmic Ca 2ϩ mediate actions of hormones, neurotransmitters (NTs), and other stimuli that activate phospholipases C␤ and C␥ (1). Conventional protein kinase C isoforms (cPKCs ␣, ␤I, ␤II, and ␥) are widely expressed effectors of Ca 2ϩ and DAG in mammalian tissues (2-5). cPKCs are translocated to membranes and activated by binding Ca 2ϩ and DAG via their respective C2 and C1 domains. Thus, cPKCs are poised to receive, amplify, and disseminate the complete spectrum of intracellular signals generated by phospholipase C activation. Accordingly, cPKCs often couple extracellular stimuli to physiological processes that are coregulated by dynamic changes in Ca 2ϩ and DAG levels. In contrast, novel PKC isoforms (nPKCs ␦, , , and ) are activated by DAG alone.Some cell functions are redundantly regulated by combinations of PKCs. However, individual cPKCs can control key aspects of homeostasis or, when misregulated, promote pathological processes. For example, PKC␣ selectively regulates cardiac contrac-

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Section: Discussionmentioning

confidence: 99%

A Calcium- and Diacylglycerol-Stimulated Protein Kinase C (PKC), Caenorhabditis elegans PKC-2, Links Thermal Signals to Learned Behavior by Acting in Sensory Neurons and Intestinal Cells

Land

Rubin

2017

Molecular and Cellular Biology

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“…Behavioral acclimation to T c is reflected in part by adaptation of the thermosensory response threshold ( T* AFD ) of the bilateral AFD sensory neuron pair (Biron et al, 2006; Clark et al, 2006; Kimura et al, 2004; Mori and Ohshima, 1995; Ramot et al, 2008; Yu et al, 2014). Measurements of intracellular calcium dynamics and temperature-evoked currents have shown that AFD depolarizes and hyperpolarizes upon warming and cooling, respectively, at temperatures warmer than T* AFD to drive thermotaxis behaviors (Clark et al, 2006; Kimura et al, 2004; Ramot et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Receptor-type Guanylyl Cyclases Confer Thermosensory Responses in C. elegans

Takeishi

Hapiak

et al. 2016

Neuron

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111

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SUMMARY Thermosensation is critical for optimal regulation of physiology and behavior. C. elegans acclimates to its cultivation temperature (Tc), and exhibits thermosensitive behaviors at temperatures relative to Tc. These behaviors are mediated primarily by the AFD sensory neurons which are extraordinarily thermosensitive, and respond to thermal fluctuations at temperatures above a Tc-determined threshold. Although cGMP signaling is necessary for thermotransduction, the thermosensors in AFD are unknown. Here we show that AFD-specific receptor guanylyl cyclases (rGCs) are instructive for thermosensation. In addition to being necessary for thermotransduction, ectopic expression of these rGCs confers highly temperature-dependent responses onto diverse cell types. We find that the temperature response threshold is determined by the rGC and cellular context, and that multiple domains contribute to their thermosensory properties. Identification of thermosensory rGCs in C. elegans provides insight into mechanisms of thermosensation and thermal acclimation, and suggests that rGCs may represent a new family of molecular thermosensors.

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“…On December 3, 2014, two research articles [59,60] were published in Neuron on the subject of C. elegans ’ ability to alter thermotaxis based on past experience. These studies built on years of work showing that CaM Kinase cascade signals to CREB and other transcription factors in the nematode [61,62].…”

Section: Introductionmentioning

confidence: 99%

“…Nematodes adapted their thermotaxis behavior, tolerating warmer temperatures if they had been incubated at higher temperatures. CMK-1 regulates this physiological set point via modulation of guanylyl cyclase gene ( gcy ) expression levels [60]. In FLP nociceptors, cytoplasmic CMK-1 promotes thermal avoidance in the face of noxious temperatures.…”

Section: Introductionmentioning

confidence: 99%

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Evolutionary and functional perspectives on signaling from neuronal surface to nucleus

Cohen

Tsien

et al. 2015

Biochemical and Biophysical Research Communications

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Reliance on Ca2+ signaling has been well-preserved through the course of evolution. While the complexity of Ca2+ signaling pathways has increased, activation of transcription factors including CREB by Ca2+/CaM-dependent kinases (CaMKs) has remained critical for long-term plasticity. In C. elegans, the CaMK family is made up of only three members, and CREB phosphorylation is mediated by CMK-1, the homologue of CaMKI. CMK-1 nuclear translocation directly regulates adaptation of thermotaxis behavior in response to changes in the environment. In mammals, the CaMK family has been expanded from three to ten members, enabling specialization of individual elements of a signal transduction pathway and increased reliance on the CaMKII subfamily. This increased complexity enables private line communication between Ca2+ sources at the cell surface and specific cellular targets. Using both new and previously published data, we review the mechanism of a γCaMKII-CaM nuclear translocation. This intricate pathway depends on a specific role for multiple Ca2+/CaM-dependent kinases and phosphatases: α/βCaMKII phosphorylates γCaMKII to trap CaM; CaN dephosphorylates γCaMKII to dispatch it to the nucleus; and PP2A induces CaM release from γCaMKII so that CaMKK and CaMKIV can trigger CREB phosphorylation. Thus, while certain basic elements have been conserved from C. elegans, evolutionary modifications offer opportunities for targeted communication, regulation of key nodes and checkpoints, and greater specificity and flexibility in signaling.

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CaMKI-Dependent Regulation of Sensory Gene Expression Mediates Experience-Dependent Plasticity in the Operating Range of a Thermosensory Neuron

Cited by 66 publications

References 35 publications

A Calcium- and Diacylglycerol-Stimulated Protein Kinase C (PKC), Caenorhabditis elegans PKC-2, Links Thermal Signals to Learned Behavior by Acting in Sensory Neurons and Intestinal Cells

A Calcium- and Diacylglycerol-Stimulated Protein Kinase C (PKC), Caenorhabditis elegans PKC-2, Links Thermal Signals to Learned Behavior by Acting in Sensory Neurons and Intestinal Cells

Receptor-type Guanylyl Cyclases Confer Thermosensory Responses in C. elegans

Evolutionary and functional perspectives on signaling from neuronal surface to nucleus

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