The Interaction between Syntaxin 1A and Cystic Fibrosis Transmembrane Conductance Regulator Cl− Channels Is Mechanistically Distinct from Syntaxin 1A-SNARE Interactions

Ganeshan, Radhika; Di, Anke; Nelson, Deborah J.; Quick, Michael W.; Kirk, Kevin L.

doi:10.1074/jbc.m211790200

Cited by 23 publications

(19 citation statements)

References 29 publications

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“…In all of these examples, the interacting domains of SNARE appear to be situated within the C-terminal a-helix that anchors the protein in the plasma membrane and the adjacent H3 a-helix that normally assembles as part of the SNARE core complex during vesicle fusion. The H3 a-helix also binds the CFTR Cl 2 channel (Naren et al, 1997;Ganeshan et al, 2003), although the association with vesicle fusion and possible roles for this interaction are less obvious. One difficulty in each of these examples rests with the amphipathic properties of the Q a -SNARE H3 a-helix: its seemingly promiscuous capacity for protein interaction has raised concerns about interpreting the physiological significance of SNARE binding with the channel proteins (Fletcher et al, 2003).…”

Section: A Unique N-terminal Domain With Overlapping Functions?mentioning

confidence: 99%

A Novel Motif Essential for SNARE Interaction with the K+ Channel KC1 and Channel Gating inArabidopsis

et al. 2010

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The SNARE (for soluble N-ethylmaleimide-sensitive factor protein attachment protein receptor) protein SYP121 (=SYR1/ PEN1) of Arabidopsis thaliana facilitates vesicle traffic, delivering ion channels and other cargo to the plasma membrane, and contributing to plant cell expansion and defense. Recently, we reported that SYP121 also interacts directly with the K + channel subunit KC1 and forms a tripartite complex with a second K + channel subunit, AKT1, to control channel gating and K + transport. Here, we report isolating a minimal sequence motif of SYP121 prerequisite for its interaction with KC1. We made use of yeast mating-based split-ubiquitin and in vivo bimolecular fluorescence complementation assays for proteinprotein interaction and of expression and electrophysiological analysis. The results show that interaction of SYP121 with KC1 is associated with a novel FxRF motif uniquely situated within the first 12 residues of the SNARE sequence, that this motif is the minimal requirement for SNARE-dependent alterations in K + channel gating when heterologously expressed, and that rescue of KC1-associated K + current of the root epidermis in syp121 mutant Arabidopsis plants depends on expression of SNARE constructs incorporating this motif. These results establish the FxRF sequence as a previously unidentified motif required for SNARE-ion channel interactions and lead us to suggest a mechanistic framework for understanding the coordination of vesicle traffic with transmembrane ion transport.

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Section: A Unique N-terminal Domain With Overlapping Functions?mentioning

confidence: 99%

A Novel Motif Essential for SNARE Interaction with the K+ Channel KC1 and Channel Gating inArabidopsis

et al. 2010

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“…Another SNARE protein, syntaxin-1A, also interacts with Ca 2ϩ and K ϩ channel subunits and functionally regulates these channels (119, 174,541,562,819). Syntaxin-1A also interacts with proteins of the ABCCx gene family, including CFTR (ABCC7), SUR1 (ABCC8), and SUR2 (ABCC9) (252,421,634). Syntaxin-1A regulates both the trafficking and gating of CTFR (791).…”

Section: Membrane Delivery and Anchoringmentioning

confidence: 99%

K_ATPChannels in the Cardiovascular System

Foster

Coetzee

2016

Physiological Reviews

204

237

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KATP channels are integral to the functions of many cells and tissues. The use of electrophysiological methods has allowed for a detailed characterization of KATP channels in terms of their biophysical properties, nucleotide sensitivities, and modification by pharmacological compounds. However, even though they were first described almost 25 years ago (Noma 1983, Trube and Hescheler 1984), the physiological and pathophysiological roles of these channels, and their regulation by complex biological systems, are only now emerging for many tissues. Even in tissues where their roles have been best defined, there are still many unanswered questions. This review aims to summarize the properties, molecular composition, and pharmacology of KATP channels in various cardiovascular components (atria, specialized conduction system, ventricles, smooth muscle, endothelium, and mitochondria). We will summarize the lessons learned from available genetic mouse models and address the known roles of KATP channels in cardiovascular pathologies and how genetic variation in KATP channel genes contribute to human disease.

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“…At the cell surface, CFTR is regulated by interactions with the soluble N-ethyl maleimide-sensitive factor attachment protein receptors (t-SNAREs) syntaxin 1A and SNAP23 (18,19). The direct association of t-SNAREs to the CFTR N terminus negatively regulates channel gating as well as membrane trafficking (18)(19)(20)(21)(22)(23)(24). CFTR channel activity can also be regulated through an intramolecular interaction between the N terminus and regulatory domain (R domain) (25,26).…”

Section: Introductionmentioning

confidence: 99%

Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR

Thelin¹,

Chen²,

Gentzsch³

et al. 2007

J. Clin. Invest.

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The role of the cystic fibrosis transmembrane conductance regulator (CFTR) as a cAMP-dependent chloride channel on the apical membrane of epithelia is well established. However, the processes by which CFTR is regulated on the cell surface are not clear. Here we report the identification of a protein-protein interaction between CFTR and the cytoskeletal filamin proteins. Using proteomic approaches, we identified filamins as proteins that associate with the extreme CFTR N terminus. Furthermore, we identified a disease-causing missense mutation in CFTR, serine 13 to phenylalanine (S13F), which disrupted this interaction. In cells, filamins tethered plasma membrane CFTR to the underlying actin network. This interaction stabilized CFTR at the cell surface and regulated the plasma membrane dynamics and confinement of the channel. In the absence of filamin binding, CFTR was internalized from the cell surface, where it prematurely accumulated in lysosomes and was ultimately degraded. Our data demonstrate what we believe to be a previously unrecognized role for the CFTR N terminus in the regulation of the plasma membrane stability and metabolic stability of CFTR. In addition, we elucidate the molecular defect associated with the S13F mutation.

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The Interaction between Syntaxin 1A and Cystic Fibrosis Transmembrane Conductance Regulator Cl− Channels Is Mechanistically Distinct from Syntaxin 1A-SNARE Interactions

Cited by 23 publications

References 29 publications

A Novel Motif Essential for SNARE Interaction with the K+ Channel KC1 and Channel Gating inArabidopsis

A Novel Motif Essential for SNARE Interaction with the K+ Channel KC1 and Channel Gating inArabidopsis

K_ATPChannels in the Cardiovascular System

Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR

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The Interaction between Syntaxin 1A and Cystic Fibrosis Transmembrane Conductance Regulator Cl− Channels Is Mechanistically Distinct from Syntaxin 1A-SNARE Interactions

Cited by 23 publications

References 29 publications

A Novel Motif Essential for SNARE Interaction with the K+ Channel KC1 and Channel Gating inArabidopsis

A Novel Motif Essential for SNARE Interaction with the K+ Channel KC1 and Channel Gating inArabidopsis

KATPChannels in the Cardiovascular System

Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR

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Product

Resources

About

K_ATPChannels in the Cardiovascular System