Stomatin modulates the activity of the Anion Exchanger 1 (AE1, SLC4A1)

Genetet, Sandrine; Desrames, Alexandra; Chouali, Youcef; Ripoche, Pierre; Lopez, Claude; Mouro-Chanteloup, Isabelle

doi:10.1038/srep46170

Cited by 24 publications

(26 citation statements)

References 42 publications

(60 reference statements)

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“…In contrast, overexpression and knockdown of the lipid-raft-associated protein stomatin led to an increase in NTCP-mediated bile acid uptake without affecting its plasma membrane localization. Interestingly, stomatin has been shown to interact and regulate multiple other membrane transporters and ion channels [17][18][19]. The effect of stomatin overexpression seems to depend on its target, and either decreases its function, such as for the glucose transporter 1 (GLUT-1) [17] or, similar to its effect on NTCP, increases transport activity, as shown for the anion exchanger 1 (AE1) [19].…”

Section: Discussionmentioning

confidence: 99%

“…Total cell lysates from HepG2 cells expressing HA-hNTCP or from control cells without NTCP (parental) were subjected to immunoprecipitation using anti-HA coupled beads, and the precipitates were subsequently analyzed by label-free quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) [10] ( Figure 1A). This paper focusses on two enriched potential partners, stomatin and chloride channel CLIC-like 1, a single-pass membrane protein associated with lipid rafts and a intracellular chloride channel, respectively [12,[16][17][18][19].…”

Section: Interaction Of Clcc1 and Stomatin With Ntcpmentioning

confidence: 99%

“…The second protein we identified is stomatin (abbreviated as STOM in the figures), a ubiquitously expressed integral membrane protein that is associated with the cytoplasmic face of the plasma membrane via its palmitoylation sites and a short hydrophobic hairpin region [15]. Stomatin has at least one cholesterol binding site, is frequently localized to cholesterol-rich lipid rafts and has previously been shown to regulate several other membrane proteins, including the glucose transporter GLUT-1 and the anion exchanger AE-1 [16][17][18][19]. We further performed functional studies to assess a potential role for CLCC1 and stomatin in NTCP regulation.…”

Section: Introductionmentioning

confidence: 99%

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The Lipid Raft Component Stomatin Interacts with the Na+ Taurocholate Cotransporting Polypeptide (NTCP) and Modulates Bile Salt Uptake

Appelman

Robin

Vogels

et al. 2020

Cells

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The sodium taurocholate cotransporting polypeptide (NTCP) is expressed at the basolateral membrane of hepatocytes, where it mediates the uptake of conjugated bile acids and forms the hepatocyte entry receptor for the hepatitis B and D virus. Here, we aimed to identify novel protein–protein interactions that could play a role in the regulation of NTCP. To this end, NTCP was precipitated from HA-tagged hNTCP-expressing HepG2 cells, and chloride channel CLIC-like 1 (CLCC1) and stomatin were identified as interacting proteins by mass spectrometry. Interaction was confirmed by co-immunoprecipitation. NTCP, CLCC1 and stomatin were found at the plasma membrane in lipid rafts, as demonstrated by a combination of immunofluorescence, cell surface biotinylation and isolation of detergent-resistant membranes. Neither CLCC1 overexpression nor its knockdown had an effect on NTCP function. However, both stomatin overexpression and knockdown increased NTCP-mediated taurocholate uptake while NTCP abundance at the plasma membrane was only increased in stomatin depleted cells. These findings identify stomatin as an interactor of NTCP and show that the interaction modulates bile salt transport.

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Section: Discussionmentioning

confidence: 99%

Section: Interaction Of Clcc1 and Stomatin With Ntcpmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Lipid Raft Component Stomatin Interacts with the Na+ Taurocholate Cotransporting Polypeptide (NTCP) and Modulates Bile Salt Uptake

Appelman

Robin

Vogels

et al. 2020

Cells

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“…In addition, STOM is part of a superfamily of proteins that contain a conserved SPFH domain. STOM has previously been shown to regulate several membrane proteins, including the glucose transporter GLUT-1, the anion exchanger AE-1, and ASICs (Brand et al, 2012; Genetet et al, 2017; Moshourab et al, 2013; Price et al, 2004; Zhang et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Insights into the molecular mechanisms underlying the inhibition of acid-sensing ion channel 3 gating by stomatin

Klipp¹,

Cullinan

Bankston

2020

Journal of General Physiology

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Stomatin (STOM) is a monotopic integral membrane protein found in all classes of life that has been shown to regulate members of the acid-sensing ion channel (ASIC) family. However, the mechanism by which STOM alters ASIC function is not known. Using chimeric channels, we combined patch-clamp electrophysiology and FRET to search for regions of ASIC3 critical for binding to and regulation by STOM. With this approach, we found that regulation requires two distinct sites on ASIC3: the distal C-terminus and the first transmembrane domain (TM1). The C-terminal site is critical for formation of the STOM–ASIC3 complex, while TM1 is required only for the regulatory effect. We then looked at the mechanism of STOM-dependent regulation of ASIC3 and found that STOM does not alter surface expression of ASIC3 or shift the pH dependence of channel activation. However, a point mutation (Q269G) that prevents channel desensitization also prevents STOM regulation, suggesting that STOM may alter ASIC3 currents by stabilizing the desensitized state of the channel. Based on these findings, we propose a model whereby STOM is anchored to the channel via a site on the distal C-terminus and stabilizes the desensitized state of the channel via an interaction with TM1.

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“…Exchanger AE-1, and ASICs (Brand et al, 2012;Genetet et al, 2017;Moshourab et al, 2013;Price et al, 47 2004;Zhang et al, 2001). 48…”

Section: Introduction 18mentioning

confidence: 99%

Insights into the molecular mechanisms underlying the inhibition of acid-sensing ion channel 3 gating by Stomatin

Klipp

Cullinan

Bankston

2019

Preprint

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7Stomatin is a monotopic integral membrane protein found in all classes of life that has been shown to 8 regulate members of the Acid-Sensing Ion Channel (ASIC) family. However, the mechanism by which 9Stomatin alters ASIC function is not known. Using chimeric channels, we combined patch clamp 10 electrophysiology and FRET to search for regions of ASIC3 critical for binding to and regulation by 11Stomatin. With this approach, we found that regulation requires two distinct sites on ASIC3: the distal C-12terminus and the first transmembrane domain. Mutation of the C-terminal site disrupts binding and 13 regulation whereas disruption of the transmembrane site eliminates functional regulation. We then 14showed that Stomatin does not alter surface expression using fluorescence imaging and a surface 15 biotinylation assay. Based on these findings, we propose a model whereby STOM is anchored to the 16 channel via a site on the distal C-terminus but alters ASIC3 gating through action on TM1. 17

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Stomatin modulates the activity of the Anion Exchanger 1 (AE1, SLC4A1)

Cited by 24 publications

References 42 publications

The Lipid Raft Component Stomatin Interacts with the Na+ Taurocholate Cotransporting Polypeptide (NTCP) and Modulates Bile Salt Uptake

The Lipid Raft Component Stomatin Interacts with the Na+ Taurocholate Cotransporting Polypeptide (NTCP) and Modulates Bile Salt Uptake

Insights into the molecular mechanisms underlying the inhibition of acid-sensing ion channel 3 gating by stomatin

Insights into the molecular mechanisms underlying the inhibition of acid-sensing ion channel 3 gating by Stomatin

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