Two PKC consensus sites on human acid-sensing ion channel 1b differentially regulate its function

Bashari, Edlira; Qadri, Yawar J.; Zhou, Zhenqi; Kapoor, Niren; Anderson, Susan J.; Meltzer, Robert H.; Fuller, Catherine M.; Benos, Dale J.

doi:10.1152/ajpcell.00200.2008

Cited by 15 publications

(17 citation statements)

References 45 publications

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“…Consistent with previous data from our laboratory in isolated pulmonary arteries and pulmonary arterial endothelial sheets (32,39), activation of PKC suppressed SOCE in PASMC. These data are in line with reports that PKC activation reduces current amplitude of human ASIC1 in glioma cells and Xenopus oocytes (3,4). Although PICK1 may contribute to PKC-mediated inhibition of SOCE, it does not appear to be required, since inhibition of PICK1 did not prevent PKC-mediated attenuation of SOCE.…”

Section: Discussionsupporting

confidence: 92%

“…PICK1 binds the COOH terminus of PKC through its PDZ domain (42) and can regulate ASIC. The effect of PKC on ASIC1 has been shown to be either stimulatory or inhibitory, depending on the PKC isoform and phosphorylation site (3,4,16,50). Consistent with previous data from our laboratory in isolated pulmonary arteries and pulmonary arterial endothelial sheets (32,39), activation of PKC suppressed SOCE in PASMC.…”

Section: Discussionsupporting

confidence: 89%

“…PICK1 binds the COOH terminus of PKC through its PDZ domain (42) and can regulate ASIC1. However, the effect of PKC on ASIC1 activity is controversial (3,4,50); therefore, we first determined the effect of PKC on SOCE. Activation of PKC␣ significantly attenuated SOCE, whereas inhibition of PKC augmented SOCE (Fig.…”

Section: Pkc Inhibits Socementioning

confidence: 99%

“…PICK1 was originally isolated by its ability to bind the COOH terminus of protein kinase C (PKC) through its PDZ domain and facilitate PKC phosphorylation of ASIC1 and ASIC2 (2,16,42). Although PKC phosphorylation leads to potentiation of ASIC2 current (2), the effect of PKC on ASIC1 activity is controversial (3,4,50). Additionally, PICK1 can bind the calcium/calmodulin-activated phosphatase, calcineurin B, and ASIC activity has been shown to be inhibited by calcineurin (5,17).…”

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confidence: 99%

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PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

Herbert

Nitta

Yellowhair

et al. 2016

American Journal of Physiology-Cell Physiology

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Herbert LM, Nitta CH, Yellowhair TR, Browning C, Gonzalez Bosc LV, Resta TC, Jernigan NL. PICK1/calcineurin suppress ASIC1-mediated Ca 2ϩ entry in rat pulmonary arterial smooth muscle cells. Am J Physiol Cell Physiol 310: C390 -C400, 2016. First published December 23, 2015; doi:10.1152/ajpcell.00091.2015.-Acidsensing ion channel 1 (ASIC1) contributes to Ca 2ϩ influx and contraction in pulmonary arterial smooth muscle cells (PASMC). ASIC1 binds the PDZ (PSD-95/Dlg/ZO-1) domain of the protein interacting with C kinase 1 (PICK1), and this interaction is important for the subcellular localization and/or activity of ASIC1. Therefore, we first hypothesized that PICK1 facilitates ASIC1-dependent Ca 2ϩ influx in PASMC by promoting plasma membrane localization. Using Duolink to determine protein-protein interactions and a biotinylation assay to assess membrane localization, we demonstrated that the PICK1 PDZ domain inhibitor FSC231 diminished the colocalization of PICK1 and ASIC1 but did not limit ASIC1 plasma membrane localization. Although stimulation of store-operated Ca 2ϩ entry (SOCE) greatly enhanced colocalization between ASIC1 and PICK1, both FSC231 and shRNA knockdown of PICK1 largely augmented SOCE. These data suggest PICK1 imparts a basal inhibitory effect on ASIC1 Ca 2ϩ entry in PASMC and led to an alternative hypothesis that PICK1 facilitates the interaction between ASIC1 and negative intracellular modulators, namely PKC and/or the calcium-calmodulin-activated phosphatase calcineurin. FSC231 limited PKC-mediated inhibition of SOCE, supporting a potential role for PICK1 in this response. Additionally, we found PICK1 inhibits ASIC1-mediated SOCE through an effect of calcineurin to dephosphorylate the channel. Furthermore, it appears PICK1/calcineurin-mediated regulation of SOCE opposes PKA phosphorylation and activation of ASIC1. Together our data suggest PKA and PICK1/calcineurin differentially regulate ASIC1-mediated SOCE and these modulatory complexes are important in determining downstream Ca 2ϩ signaling.store-operated calcium entry; FSC231; DEG/ENaC; Duolink; PKA; PKC ACID-SENSING ION CHANNELS (ASIC) belong to the degenerin/ epithelial sodium channel (DEG/ENaC) superfamily, which includes several amiloride-sensitive cation channels. Significant progress has been made in understanding the structure and function of ASIC in the nervous system; however, several questions remain regarding their physiological importance in other tissues. There is an emerging role for both ENaC and ASIC in vascular smooth muscle and endothelial cells from a variety of vascular beds (8, 10 -12, 19, 20, 25, 33, 46). Consistent with a physiological role of ASIC in the vasculature, our laboratory has recently shown that ASIC1 is an important facilitator of G protein-coupled receptor signaling via store-operated Ca 2ϩ entry (SOCE) in pulmonary arterial smooth muscle cells (PASMC) (21, 22). Furthermore, ASIC1-mediated Ca 2ϩ entry in PASMC appears to be an important constituent of both the active vasoconstrictor and vascular remodelin...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Section: Pkc Inhibits Socementioning

confidence: 99%

mentioning

confidence: 99%

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PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

Herbert

Nitta

Yellowhair

et al. 2016

American Journal of Physiology-Cell Physiology

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“…It is clear that humans express a subunit homologous to mouse and rat ASIC1a (ACCN2 transcript variant 2), which has been referred to as both human ASIC1a and human ASIC1b (27,32,33). In addition, ACCN2 transcript variant 1 has been identified in humans (32).…”

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confidence: 99%

Identification of a Calcium Permeable Human Acid-sensing Ion Channel 1 Transcript Variant

Hoagland

Sherwood

Lee

et al. 2010

Journal of Biological Chemistry

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The acid-sensing ion channels (ASICs) are proton-gated cation channels activated when extracellular pH declines. In rodents, the Accn2 gene encodes transcript variants ASIC1a and ASIC1b, which differ in the first third of the protein and display distinct channel properties. In humans, ACCN2 transcript variant 2 (hVariant 2) is homologous to mouse ASIC1a. In this article, we study two other human ACCN2 transcript variants. Human ACCN2 transcript variant 1 (hVariant 1) is not present in rodents and contains an additional 46 amino acids directly preceding the proposed channel gate. We report that hVariant 1 does not produce proton-gated currents under normal conditions when expressed in heterologous systems. We also describe a third human ACCN2 transcript variant (hVariant 3) that is similar to rodent ASIC1b. hVariant 3 is more abundantly expressed in dorsal root ganglion compared with brain and shows basic channel properties analogous to rodent ASIC1b. Yet, proton-gated currents from hVariant 3 are significantly more permeable to calcium than either hVariant 2 or rodent ASIC1b, which shows negligible calcium permeability. hVariant 3 also displays a small acid-dependent sustained current. Such a sustained current is particularly intriguing as ASIC1b is thought to play a role in sensory transduction in rodents. In human DRG neurons, hVariant 3 could induce sustained calcium influx in response to acidic pH and make a major contribution to acid-dependent sensations, such as pain.The acid-sensing ion channels (ASICs) 4 are a family of proton-gated cation channels expressed in neurons throughout the central and peripheral nervous system (1). There are four ASIC genes (Accn1-4) that produce at least six individual ASIC subunits in rodents (ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, and ASIC4). ASIC subunits have a characteristic topology with two transmembrane domains separated by a large cysteine-rich extracellular region (2, 3). Three individual ASIC subunits associate to form functional cation channels that are activated by decreases in extracellular pH (4, 5). ASIC currents are typically transient, inactivate even in the continued presence of acidic pH, and (except for ASIC1a) are not substantially permeable to calcium (6). The specific properties of an ASIC current, such as the pH necessary for activation and the kinetics of inactivation, are defined by the subunit composition of the channel (7). In the central nervous system, the ASIC1a subunit plays an important role (8). Genetic disruption or pharmacological inhibition of ASIC1a affects learning and memory, fear-related behaviors, pain, depression, and seizure duration in rodents (9 -15). ASIC1a also contributes to neuronal damage after cerebral ischemia in mice and mediates neuronal death following prolonged acidosis (16 -19). ASIC1a is thought to play a prominent role in neuronal death because it is uniquely permeable to calcium compared with other ASICs (16,20,21).In rodents, the Accn2 gene encodes both ASIC1a and ASIC1b. ASIC1b is a transcript variant expressed...

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Mechanisms involved in α_1B‐adrenoceptor desensitization

2011

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Summarya 1B -Adrenergic receptors mediate many of the actions of the natural catecholamines, adrenaline and noradrenaline. They belong to the seven transmembrane domains G protein-coupled receptor superfamily and exert their actions mainly through activation of Gq proteins and phosphoinositide turnover/calcium signaling. Many hormones and neurotransmitters are capable of inducing a 1B -adrenergic receptor phosphorylation and desensitization; among them: adrenaline and noradrenaline, phorbol esters, endothelin-I, bradykinin, lysophosphatidic acid, insulin, EGF, PDGF, IGF-I, TGF-b, and estrogens. Key protein kinases for these effects are G protein coupled receptor kinases and protein kinase C. The lipid/protein kinase, phosphoinositide-3 kinase also appears to play a key role, acting upstream of protein kinase C. In addition to the agents employed for cells stimulation, we observed that paracrine/autocrine mediators also participate; these processes include EGF transactivation and sphingosine-1-phosphate production and action. The complex regulation of these receptors unlocks opportunities for therapeutic intervention.

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Two PKC consensus sites on human acid-sensing ion channel 1b differentially regulate its function

Cited by 15 publications

References 45 publications

PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

Identification of a Calcium Permeable Human Acid-sensing Ion Channel 1 Transcript Variant

Mechanisms involved in α_1B‐adrenoceptor desensitization

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Two PKC consensus sites on human acid-sensing ion channel 1b differentially regulate its function

Cited by 15 publications

References 45 publications

PICK1/calcineurin suppress ASIC1-mediated Ca2+ entry in rat pulmonary arterial smooth muscle cells

PICK1/calcineurin suppress ASIC1-mediated Ca2+ entry in rat pulmonary arterial smooth muscle cells

Identification of a Calcium Permeable Human Acid-sensing Ion Channel 1 Transcript Variant

Mechanisms involved in α1B‐adrenoceptor desensitization

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PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

PICK1/calcineurin suppress ASIC1-mediated Ca²⁺ entry in rat pulmonary arterial smooth muscle cells

Mechanisms involved in α_1B‐adrenoceptor desensitization