Gγ in<i>Dictyostelium</i>: Its Role in Localization of Gβγ to the Membrane Is Required for Chemotaxis in Shallow Gradients

Zhang, Ning; Lan, Yu; Devreotes, Peter N.

doi:10.1091/mbc.12.10.3204

Cited by 47 publications

(42 citation statements)

References 42 publications

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“…Western blotting analysis was performed as described with minor modifications (17). Briefly, CCR1:TRPV1͞HEK293 cells were homogenized by sonication.…”

Section: Methodsmentioning

confidence: 99%

A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1

Zhang

Inan

Cowan

et al. 2005

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

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225

174

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Pain, a critical component of host defense, is one hallmark of the inflammatory response. We therefore hypothesized that pain might be exacerbated by proinflammatory chemokines. To test this hypothesis, CCR1 was cotransfected into human embryonic kidney (HEK)293 cells together with transient receptor potential vanilloid 1 (TRPV1), a cation channel required for certain types of thermal hyperalgesia. In these cells, capsaicin and anandamide induced Ca2+ influx mediated by TRPV1. When CCR1:TRPV1/HEK293 cells were pretreated with CCL3, the sensitivity of TRPV1, as indicated by the Ca2+ influx, was increased ≈3-fold. RT-PCR analysis showed that a spectrum of chemokine and cytokine receptors is expressed in rat dorsal root ganglia (DRG). Immunohistochemical staining of DRG showed that CCR1 is coexpressed with TRPV1 in >85% of small-diameter neurons. CCR1 on DRG neurons was functional, as demonstrated by CCL3-induced Ca2+ ion influx and PKC activation. Pretreatment with CCL3 enhanced the response of DRG neurons to capsaicin or anandamide. This sensitization was inhibited by pertussis toxin, U73122, or chelerythrine chloride, inhibitors of Gi-protein, phospholipase C, and protein kinase C, respectively. Intraplantar injection of mice with CCL3 decreased their hot-plate response latency. That a proinflammatory chemokine, by interacting with its receptor on small-diameter neurons, sensitizes TRPV1 reveals a previously undescribed mechanism of receptor cross-sensitization that may contribute to hyperalgesia during inflammation

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“…Western blotting analysis was performed as described with minor modifications (17). Briefly, CCR1:TRPV1͞HEK293 cells were homogenized by sonication.…”

Section: Methodsmentioning

confidence: 99%

A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1

Zhang

Inan

Cowan

et al. 2005

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

Self Cite

225

174

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“…Assays of GiPCR-mediated inhibition of cAMP accumulation were conducted, as described by Zhang et al and Amersham's protocol (Piscataway, NJ) (29). Briefly, cells were starved for 3 h in serum-free medium before the experiments, harvested by trypsin treatment, and resuspended in 0.1% BSA/DMEM at 1 ϫ 10 7 /ml.…”

Section: Assays For Gipcr-mediated Inhibition Of Camp Accumulationmentioning

confidence: 99%

Proinflammatory Chemokines, Such as C-C Chemokine Ligand 3, Desensitize μ-Opioid Receptors on Dorsal Root Ganglia Neurons

Zhang

Rogers

Oppenheim

2004

The Journal of Immunology

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110

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Pain is one of the hallmarks of inflammation. Opioid receptors mediate antipain responses in both the peripheral nervous system and CNS. In the present study, pretreatment of CCR1:μ-opioid receptor/HEK293 cells with CCL3 (MIP-1α) induced internalization of μ-opioid receptors and severely impaired the μ-opioid receptor-mediated inhibition of cAMP accumulation. Immunohistochemical staining showed that CCR1 and μ-opioid receptors were coexpressed on small to medium diameter neurons in rat dorsal root ganglion. Analysis of ligand-induced calcium flux showed that both types of receptors were functional. Pretreatment of neurons with CCL3 exhibited an impaired [d-Ala2,N-MePhe4,Gly-o15]enkephalin-elicited calcium response, indicative of the heterologous desensitization of μ-opioid receptors. Other chemokines, such as CCL2, CCL5, and CXCL8, exhibited similar inhibitory effects. Our data indicate that proinflammatory chemokines are capable of desensitizing μ-opioid receptors on peripheral sensory neurons, providing a novel potential mechanism for peripheral inflammation-induced hyperalgesia.

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“…The pathway leading to ACA activation is mediated through G␤␥ subunits (13,14) and requires input from both PI3K (15) and the target of rapamycin complex 2 (TORC2) (16 -20). In addition, once synthesized, cAMP levels are regulated directly by the intracellular phosphodiesterase, RegA (21), and indirectly by the MAP kinase ERK2, which is thought to inhibit RegA (22).…”

mentioning

confidence: 99%

Direct Biochemical Measurements of Signal Relay during Dictyostelium Development

Das

Rericha

Bagorda

et al. 2011

Journal of Biological Chemistry

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Upon starvation, individual Dictyostelium discoideum cells enter a developmental program that leads to collective migration and the formation of a multicellular organism. The process is mediated by extracellular cAMP binding to the G proteincoupled cAMP receptor 1, which initiates a signaling cascade leading to the activation of adenylyl cyclase A (ACA), the synthesis and secretion of additional cAMP, and an autocrine and paracrine activation loop. The release of cAMP allows neighboring cells to polarize and migrate directionally and form characteristic chains of cells called streams. We now report that cAMP relay can be measured biochemically by assessing ACA, ERK2, and TORC2 activities at successive time points in development after stimulating cells with subsaturating concentrations of cAMP. We also find that the activation profiles of ACA, ERK2, and TORC2 change in the course of development, with later developed cells showing a loss of sensitivity to the relayed signal. We examined mutants in PKA activity that have been associated with precocious development and find that this loss in responsiveness occurs earlier in these mutants. Remarkably, we show that this loss in sensitivity correlates with a switch in migration patterns as cells transition from streams to aggregates. We propose that as cells proceed through development, the cAMP-induced desensitization and down-regulation of cAMP receptor 1 impacts the sensitivities of chemotactic signaling cascades leading to changes in migration patterns.The directed migration of individual cells or chains or sheets of cells requires cells to transduce external cues into internal signals that regulate cytoskeletal reorganization and cell polarity. Signal transduction is important during development where the transition from single to collective cell migration is regulated by multiple external cues (1). Cell-cell communication, a process that can be manifested through the relay of external chemical signals (2, 3), is critical for a wide range of developmental processes including the survival of the social amoebae Dictyostelium discoideum.Upon starvation, Dictyostelium cells enter a developmental program leading to the transition from cells operating individually to groups of cells operating as a population. Aggregation of starving cells is controlled by signaling centers that emit periodic pulses of 3Ј-5Ј-cAMP. This process is mediated by the binding of extracellular cAMP to the G protein-coupled receptor cAR1, 3 which initiates a signaling cascade leading to, among other things, the activation of ACA (4). When ACA is first activated, rapid cAMP synthesis leads to a burst in internal cAMP levels. Although part of the synthesized cAMP remains inside cells to activate PKA and regulate gene expression, the majority of it is rapidly secreted (5-7). The secreted cAMP binds to cAR1 and, in an autocrine and paracrine amplification step, results in the production and secretion of more cAMP (2, 3). For a spatially extended cell population, the stimulated release of cAMP result...

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Gγ inDictyostelium: Its Role in Localization of Gβγ to the Membrane Is Required for Chemotaxis in Shallow Gradients

Cited by 47 publications

References 42 publications

A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1

A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1

Proinflammatory Chemokines, Such as C-C Chemokine Ligand 3, Desensitize μ-Opioid Receptors on Dorsal Root Ganglia Neurons

Direct Biochemical Measurements of Signal Relay during Dictyostelium Development

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