Protein Kinase C Stimulates the Acid-sensing Ion Channel ASIC2a via the PDZ Domain-containing Protein PICK1

Baron, Anne; Deval, Emmanuel; Salinas, Miguel; Lingueglia, Éric; Voilley, Nicolas; Lazdunski, Michel

doi:10.1074/jbc.m208848200

Cited by 110 publications

(103 citation statements)

References 74 publications

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“…PICK1 is a scaffold protein to control trafficking of several membrane receptors, including AMPA receptor and ASIC, and has been implicated to function in nervous system and male fertility [17,19,20,42]. Here, we identify PICK1 as a novel negative regulator of TGF-β signaling by modulating subcellular localization and trafficking of TβRI.…”

Section: Discussionmentioning

confidence: 88%

“…As a peripheral protein, PICK1 has been reported to interact with a series of membrane proteins including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) [13][14][15][16], acid-sensing ion channel (ASICs) [17] and ErbB2/Her-2 [18]. In most of the cases, PICK1 acts as a critical regulator of membrane receptors' subcellular trafficking to modulate neural processes such as learning and memory [19,20].…”

Section: Introductionmentioning

confidence: 99%

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PICK1 promotes caveolin-dependent degradation of TGF-β type I receptor

Zhao

Wang

et al. 2012

Cell Res

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Protein that interacts with C kinase 1 (PICK1) is a critical mediator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking in neural synapses. However, its ubiquitous expression suggests that it may have other non-neural functions. Here we show that PICK1 antagonizes transforming growth factor beta (TGF-β) signaling by targeting TGF-β type I receptor (TβRI) for degradation. Biochemical analyses reveal that PICK1 directly interacts with the C-terminus of TβRI via its PDZ domain and acts as a scaffold protein to enhance the interaction between TβRI and caveolin-1, leading to enhanced lipid raft/caveolae localization. Therefore, PICK1 increases caveolin-mediated endocytosis, ubiquitination and degradation of TβRI. Moreover, a negative correlation between PICK1 expression and TβRI or phospho-Smad2 levels is observed in human breast tumors, indicating that PICK1 may participate in breast cancer development through inhibition of TGF-β signaling. Our findings reveal a non-neural function of PICK1 as an important negative regulator of TGF-β signaling.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

PICK1 promotes caveolin-dependent degradation of TGF-β type I receptor

Zhao

Wang

et al. 2012

Cell Res

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“…For instance, PICK1 binds to the C-termini of several isoforms of the ASIC family of proton-gated ion channels (ASIC1a, 2a, and 2b) via its PDZ domain (Duggan et al, 2002;Hruska-Hageman et al, 2002). Further, PICK1 is believed to target activated PKC␣ to ASIC2a, thereby leading to the phosphorylation of the channel in its cytoplasmic tail and to the potentiation of ASIC2a currents (Baron et al, 2002a). Considering that parkin promotes PICK1 monoubiquitination, we hypothesized that it might influence the ability of PICK1 to potentiate ASIC2a activity.…”

mentioning

confidence: 99%

Parkin-mediated Monoubiquitination of the PDZ Protein PICK1 Regulates the Activity of Acid-sensing Ion Channels

Joch

Ase

Chen

et al. 2007

MBoC

127

101

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Mutations in the parkin gene result in an autosomal recessive juvenile-onset form of Parkinson's disease. As an E3 ubiquitin-ligase, parkin promotes the attachment of ubiquitin onto specific substrate proteins. Defects in the ubiquitination of parkin substrates are therefore believed to lead to neurodegeneration in Parkinson's disease. Here, we identify the PSD-95/Discs-large/Zona Occludens-1 (PDZ) protein PICK1 as a novel parkin substrate. We find that parkin binds PICK1 via a PDZ-mediated interaction, which predominantly promotes PICK1 monoubiquitination rather than polyubiquitination. Consistent with monoubiquitination and recent work implicating parkin in proteasome-independent pathways, parkin does not promote PICK1 degradation. However, parkin regulates the effects of PICK1 on one of its other PDZ partners, the acid-sensing ion channel (ASIC). Overexpression of wild-type, but not PDZ binding-or E3 ubiquitinligase-defective parkin abolishes the previously described, protein kinase C-induced, PICK1-dependent potentiation of ASIC2a currents in non-neuronal cells. Conversely, the loss of parkin in hippocampal neurons from parkin knockout mice unmasks prominent potentiation of native ASIC currents, which is normally suppressed by endogenous parkin in wild-type neurons. Given that ASIC channels contribute to excitotoxicity, our work provides a mechanism explaining how defects in parkin-mediated PICK1 monoubiquitination could enhance ASIC activity and thereby promote neurodegeneration in Parkinson's disease. INTRODUCTIONParkinson's disease (PD) is characterized by the selective and progressive loss of midbrain dopamine neurons resulting in motor dysfunction and disability. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism, which accounts for a large proportion of genetically linked PD cases (Kitada et al., 1998). Parkin encodes a 465-amino acid protein (ϳ52 kDa) that is expressed in multiple tissues and functions in the ubiquitin (Ub) system as an E3 Ub-ligase (Shimura et al., 2000). Ubiquitination of substrate proteins is a tightly regulated process, requiring the combined activity of three enzymes: an E1 Ub-activating enzyme, E2 Ub-conjugating enzymes, and E3 Ub-ligases (Hershko and Ciechanover, 1998). E3 Ub-ligases bind substrate proteins and therefore regulate and confer specificity to the ubiquitination reaction. Typically, ubiquitination leads to the assembly of a K48-linked polyubiquitin chain on the substrate, which targets it for degradation by the 26S proteasome, a large multimeric proteolytic complex (Voges et al., 1999). Accordingly, defects in parkin-mediated ubiquitination have been proposed to result in the failure to target parkin substrates to the proteasome for degradation (Kahle et al., 2000;Feany and Pallanck, 2003;Giasson and Lee, 2003). The ensuing accumulation of parkin substrates is believed, in turn, to induce the cellular toxicity and dopamine neuron loss seen in PD. Although numerous parkin substrates have been identified (Zhang et al., 2000;Chung et al., 2001...

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“…Several observations indicate that ASICs are located post-synaptically, especially on dendritic spines, although they can be found also on dendrites and cell bodies [1,[8][9][10]. It has been shown that ASIC subunits interact with scaffolding proteins, such as post-synaptic density protein 95 and protein interacting with C-kinase-1 [10][11][12].…”

mentioning

confidence: 99%

“…In order to examine the role of ASIC1a in mGlu receptordependent LTD and intrinsic excitability at the hippocampal pyramidal neurons Schaffer collateral-CA1 synapse we used psalmotoxin-1 (PcTx1), a selective inhibitor of ASIC1a channels [12,[20][21][22]. We have also investigated the underlying biochemical mechanisms involved in the interplay between group I mGlu receptors and ASIC1a.…”

mentioning

confidence: 99%

Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus

Mango

Braksator

Battaglia

et al. 2017

Pharmacological Research

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a b s t r a c tAcid-sensing ion channels (ASICs), members of the degenerin/epithelial Na + channel superfamily, are widely distributed in the mammalian nervous system. ASIC1a is highly permeable to Ca 2+ and are thought to be important in a variety of physiological processes, including synaptic plasticity, learning and memory. To further understand the role of ASIC1a in synaptic transmission and plasticity, we investigated metabotropic glutamate (mGlu) receptor-dependent long-term depression (LTD) in the hippocampus. We found that ASIC1a channels mediate a component of LTD in P30-40 animals, since the ASIC1a selective blocker psalmotoxin-1 (PcTx1) reduced the magnitude of LTD induced by application of the group I mGlu receptor agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) or induced by paired-pulse low frequency stimulation (PP-LFS). Conversely, PcTx1 did not affect LTD in P13-18 animals. We also provide evidence that ASIC1a is involved in group I mGlu receptor-induced increase in action potential firing. However, blockade of ASIC1a did not affect DHPG-induced polyphosphoinositide hydrolysis, suggesting the involvement of some other molecular partners in the functional crosstalk between ASIC1a and group I mGlu receptors. Notably, PcTx1 was able to prevent the increase in GluA1 S845 phosphorylation at the post-synaptic membrane induced by group I mGlu receptor activation. These findings suggest a novel function of ASIC1a channels in the regulation of group I mGlu receptor synaptic plasticity and intrinsic excitability.

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Protein Kinase C Stimulates the Acid-sensing Ion Channel ASIC2a via the PDZ Domain-containing Protein PICK1

Cited by 110 publications

References 74 publications

PICK1 promotes caveolin-dependent degradation of TGF-β type I receptor

PICK1 promotes caveolin-dependent degradation of TGF-β type I receptor

Parkin-mediated Monoubiquitination of the PDZ Protein PICK1 Regulates the Activity of Acid-sensing Ion Channels

Acid-sensing ion channel 1a is required for mGlu receptor dependent long-term depression in the hippocampus

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