Pickpocket Is a DEG/ENaC Protein Required for Mechanical Nociception in Drosophila Larvae

Zhong, Lixian; Hwang, Richard Y.; Tracey, W. Daniel

doi:10.1016/j.cub.2009.12.057

Cited by 246 publications

(321 citation statements)

References 36 publications

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“…To verify our ppk1 genetic approaches, we first confirmed the effects of our ppk1 loss of function (ppk1 ESB ) mutants on previously published behavioral phenotypes (16,18). As shown in Fig.…”

Section: Class IV Md Sensory Neurons Contain Multiple Acid-sensingsupporting

confidence: 52%

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Pickpocket1 Is an Ionotropic Molecular Sensory Transducer

Boiko

Kucher

Stockand³

et al. 2012

Journal of Biological Chemistry

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Background: Ion channels are candidate molecules for transforming external stimuli into neural activity during sensory perception. Results: Pickpocket1 encodes an acid-sensing ion channel (ASIC) that is sufficient to drive neural activity in sensory neurons. Conclusion:The perception of external acid by Pickpocket1 channels is sufficient to produce phasic sensory neuron activity. Significance: ASIC channels can function as molecular sensory transducers in sensory neurons.

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Section: Class IV Md Sensory Neurons Contain Multiple Acid-sensingsupporting

confidence: 52%

“…Nociception Assay-Nociceptive responses to noxious mechanical stimuli were assayed using a standard protocol (2,18). In brief, third instar larvae in the wandering stage were exposed to a transient, noxious mechanical stimulus applied to the third, fourth, or fifth segment of the abdominal region with a 46-mN Von Frey filament.…”

Section: Methodsmentioning

confidence: 99%

Pickpocket1 Is an Ionotropic Molecular Sensory Transducer

Boiko

Kucher

Stockand³

et al. 2012

Journal of Biological Chemistry

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“…Class IV da neurons have been reported to detect noxious thermal (47) and mechanical stimuli (48,49), triggering larvae to engage in escape behaviors to evade predators such as parasitoid wasps (50,51). Previous studies have shown that noxious mechanical stimulation to the middle segments of third-instar larvae results in a reproducible, dorsalventral rolling escape behavior (51).…”

Section: Khc Muta Larvae Display No Synaptotagmin Aggregates and Mildmentioning

confidence: 99%

Role of kinesin-1–based microtubule sliding in Drosophila nervous system development

Winding

Kelliher

Lü

et al. 2016

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

102

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The plus-end microtubule (MT) motor kinesin-1 is essential for normal development, with key roles in the nervous system. Kinesin-1 drives axonal transport of membrane cargoes to fulfill the metabolic needs of neurons and maintain synapses. We have previously demonstrated that kinesin-1, in addition to its well-established role in organelle transport, can drive MT-MT sliding by transporting "cargo" MTs along "track" MTs, resulting in dramatic cell shape changes. The mechanism and physiological relevance of this MT sliding are unclear. In addition to its motor domain, kinesin-1 contains a second MT-binding site, located at the C terminus of the heavy chain. Here, we mutated this C-terminal MT-binding site such that the ability of kinesin-1 to slide MTs is significantly compromised, whereas cargo transport is unaffected. We introduced this mutation into the genomic locus of kinesin-1 heavy chain (KHC), generating the Khc mutA allele. Khc mutA neurons displayed significant MT sliding defects while maintaining normal transport of many cargoes. Using this mutant, we demonstrated that MT sliding is required for axon and dendrite outgrowth in vivo. Consistent with these results, Khc mutA flies displayed severe locomotion and viability defects. To test the role of MT sliding further, we engineered a chimeric motor that actively slides MTs but cannot transport organelles. Activation of MT sliding in Khc mutA neurons using this chimeric motor rescued axon outgrowth in cultured neurons and in vivo, firmly establishing the role of sliding in axon outgrowth. These results demonstrate that MT sliding by kinesin-1 is an essential biological phenomenon required for neuronal morphogenesis and normal nervous system development.kinesin-1 | microtubules | Drosophila | axon outgrowth | dendrite outgrowth N eurons are the basic unit of the nervous system, forming vast networks throughout the body that communicate using receptorligand machinery located in long cellular projections called axons and dendrites. Learning how these processes form is key to understanding the early development and pathology of the nervous system. Microtubules (MTs) and actin microfilaments have been implicated in neurite outgrowth, with many studies focusing on the growth cone at the tip of the axon. Previous models suggest that the driving forces for neurite outgrowth are MT polymerization and the treadmilling of F-actin (1, 2). However, other studies demonstrate that F-actin is dispensable to outgrowth and neurites extend even in the absence of F-actin (3-5).Our group has found that the motor protein kinesin-1 can rearrange the MT network by sliding MTs against each other (6). We have shown that kinesin-1 is required for MT sliding in cultured neurons and kinesin-1 depletion inhibits both neurite outgrowth and regeneration (7,8). Additionally, we have observed MT sliding in axons as well as MTs pushing on the axon tip (9). Recent studies from other groups have also implicated MT translocation in axon extension and dendritic organization (10-12). Based on th...

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“…These studies identified three restricted neuronal expression patterns, where SPR expression in SPR mutants can restore, or expression of mSP can induce the SP response. These neurons are defined by the expression of the sex-determination genes doublesex (dsx) and fruitless ( fru), and of pickpocket ( ppk), a DEG/ENaC channel involved in nociception [21,22,24,25]. In both the central nervous system and PNS, dsx and fru are expressed in approximately 700 and approximately 2000 neurons, respectively, in characteristic patterns, while ppk is expressed exclusively in a subset of peripheral nervous system (PNS) neurons [21,24,[26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Multiple pathways mediate the sex-peptide-regulated switch in female Drosophila reproductive behaviours

et al. 2013

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Male-derived sex-peptide (SP) induces profound changes in the behaviour of Drosophila females, resulting in decreased receptivity to further mating and increased egg laying. SP can mediate the switch in female reproductive behaviours via a G protein-coupled receptor, SPR, in neurons expressing fruitless, doublesex and pickpocket. Whether SPR is the sole receptor and whether SP induces the postmating switch in a single pathway has not, to our knowledge been tested. Here we report that the SP response can be induced in the absence of SPR when SP is ectopically expressed in neurons or when SP, transferred by mating, can access neurons through a leaky blood brain barrier. Membrane-tethered SP can induce oviposition via doublesex, but not fruitless and pickpocket neurons in SPR mutant females. Although pickpocket and doublesex neurons rely on G(o) signalling to reduce receptivity and induce oviposition, G(o) signalling in fruitless neurons is required only to induce oviposition, but not to reduce receptivity. Our results show that SP's action in reducing receptivity and inducing oviposition can be separated in fruitless and doublesex neurons. Hence, the SP-induced postmating switch incorporates shared, but also distinct circuitry of fruitless, doublesex and pickpocket neurons and additional receptors.

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Pickpocket Is a DEG/ENaC Protein Required for Mechanical Nociception in Drosophila Larvae

Cited by 246 publications

References 36 publications

Pickpocket1 Is an Ionotropic Molecular Sensory Transducer

Pickpocket1 Is an Ionotropic Molecular Sensory Transducer

Role of kinesin-1–based microtubule sliding in Drosophila nervous system development

Multiple pathways mediate the sex-peptide-regulated switch in female Drosophila reproductive behaviours

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