The “tunneling” mode of biological carrier-mediated transport

Fröhlich, Otto

doi:10.1007/bf01872834

Cited by 32 publications

(17 citation statements)

References 41 publications

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“…Another secondary carrier that may be capable of exhibiting channel-like properties is the KefC protein of E. coli (13), which is a member of the CPA2 family (TC 2.A.37). "Tunneling" of ions and other solutes through carriers with little or no conformational change has been discussed (42). Again, the more complicated carrier-type mechanism, which appears to be relevant under most physiological conditions, provides the basis for classifying these proteins (i.e., as class 2 carriers rather than class 1 channels).…”

Section: Families Of Transportersmentioning

confidence: 99%

A Functional-Phylogenetic Classification System for Transmembrane Solute Transporters

Saier

2000

Microbiol Mol Biol Rev

748

642

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SUMMARY A comprehensive classification system for transmembrane molecular transporters has been developed and recently approved by the transport panel of the nomenclature committee of the International Union of Biochemistry and Molecular Biology. This system is based on (i) transporter class and subclass (mode of transport and energy coupling mechanism), (ii) protein phylogenetic family and subfamily, and (iii) substrate specificity. Almost all of the more than 250 identified families of transporters include members that function exclusively in transport. Channels (115 families), secondary active transporters (uniporters, symporters, and antiporters) (78 families), primary active transporters (23 families), group translocators (6 families), and transport proteins of ill-defined function or of unknown mechanism (51 families) constitute distinct categories. Transport mode and energy coupling prove to be relatively immutable characteristics and therefore provide primary bases for classification. Phylogenetic grouping reflects structure, function, mechanism, and often substrate specificity and therefore provides a reliable secondary basis for classification. Substrate specificity and polarity of transport prove to be more readily altered during evolutionary history and therefore provide a tertiary basis for classification. With very few exceptions, a phylogenetic family of transporters includes members that function by a single transport mode and energy coupling mechanism, although a variety of substrates may be transported, sometimes with either inwardly or outwardly directed polarity. In this review, I provide cross-referencing of well-characterized constituent transporters according to (i) transport mode, (ii) energy coupling mechanism, (iii) phylogenetic grouping, and (iv) substrates transported. The structural features and distribution of recognized family members throughout the living world are also evaluated. The tabulations should facilitate familial and functional assignments of newly sequenced transport proteins that will result from future genome sequencing projects.

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Section: Families Of Transportersmentioning

confidence: 99%

A Functional-Phylogenetic Classification System for Transmembrane Solute Transporters

Saier

2000

Microbiol Mol Biol Rev

748

642

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“…As summarized by Frohlich [7], Cl -conductance (measured as valinomycin-triggered net K efflux) did not require extracellular Cl -, and increased without saturation proportionate to increasing symmetrical [Cl -] or with either variant of unilateral increase in the presence of fixed contralateral [Cl -]. Anion selectivity (as rank order of rates) differed for conductance and exchange, although anion selectivity of DIDS-sensitive and DIDS-insensitive components of conductance was indistinguishable.…”

Section: Ae1 As Mediator Of Dids-sensitive Anion Conductance In the Rmentioning

confidence: 86%

“…This Clconductance has been measured largely by net flux studies in rate-limiting conditions conferred by addition of cationophore, but the mechanism of the hypothesized AE1-mediated conductance has been unclear. As evidence favoring a "slippage" mechanism has not been forthcoming, a "tunneling" mechanism has been proposed [7]. In the time since, uncoupled leak conductances accompanying ion transport have been identified for cotransporters of amino acids, neurotransmitters, and metals, and most recently (in the presence of polyatomic anions) in CLC Cl -/H + exchangers [45] and SLC26 Cl -/anion exchangers [46].…”

Section: Discussionmentioning

confidence: 99%

“…It has long been assumed that red cell anion exchange and anion conductance are both mediated by AE1, since both anion exchange and conductance exhibit parallel sensitivities to the irreversible stilbene disulfonate inhibitor 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) [2] and the reversible inhibitor 4,4′-diintrostilbene-2,2′-disulfonic acid (DNDS) [7]. The complications incurred by attribution of a conductive pathway to a normally electroneutral anion exchanger with an apparently obligatory sequential ("ping-pong") mechanism gave rise to postulates of "slippage" (a stoichiometrically uncoupled or loosely coupled transporter-like translocation across the lipid bilayer permeability barrier of the empty anion binding site) or "tunneling" (a channel-like conductive anion transfer following an unusual gating event, or in the absence of any conformational change in the polypeptide).…”

Section: Introductionmentioning

confidence: 99%

“…The complications incurred by attribution of a conductive pathway to a normally electroneutral anion exchanger with an apparently obligatory sequential ("ping-pong") mechanism gave rise to postulates of "slippage" (a stoichiometrically uncoupled or loosely coupled transporter-like translocation across the lipid bilayer permeability barrier of the empty anion binding site) or "tunneling" (a channel-like conductive anion transfer following an unusual gating event, or in the absence of any conformational change in the polypeptide). Several lines of evidence have been advanced against the "slippage" mechanism [8;9;10], and the data have been considered compatible with "tunneling" [7].…”

Section: Introductionmentioning

confidence: 99%

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Reduced DIDS-sensitive chloride conductance in Ae1−/− mouse erythrocytes

Alper

Vandorpe

Peters

et al. 2008

Blood Cells, Molecules, and Diseases

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The resting membrane potential of the human erythrocyte is largely determined by a constitutive Cl -conductance ∼100-fold greater than the resting cation conductance. The 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS)-sensitive electroneutral Cl -transport mediated by the human erythroid Cl -/HCO 3 -exchanger, AE1 (SLC4A1, band 3) is ≥10,000-fold greater than can be accounted for by the Cl -conductance of the red cell. The molecular identities of conductive anion pathways across the red cell membrane remain poorly defined. We have examined red cell Cl -conductance in the Ae1 -/-mouse as a genetic test of the hypothesis that Ae1 mediates DIDSsensitive Cl -conductance in mouse red cells. We report here that wildtype mouse red cell membrane potential resembles that of human red cells in the predominance of its Cl -conductance. We show with four technical approaches that the DIDS-sensitive component of erythroid Cl -conductance is reduced or absent from Ae1 -/-red cells. These results are consistent with the hypothesis that the Ae1 anion exchanger polypeptide can operate infrequently in a conductive mode. However, the fragile red cell membrane of the Ae1 -/-mouse red cell exhibits reduced abundance or loss of multiple polypeptides. Thus, loss of one or more distinct, DIDS-sensitive anion channel polypeptide(s) from the Ae1 -/-red cell membrane cannot be ruled out as an explanation for the reduced DIDS-sensitive anion conductance.

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Anion Exchangers of Mammalian Cell Membranes

Cabantchik

1994

Biomembranes

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The “tunneling” mode of biological carrier-mediated transport

Cited by 32 publications

References 41 publications

A Functional-Phylogenetic Classification System for Transmembrane Solute Transporters

A Functional-Phylogenetic Classification System for Transmembrane Solute Transporters

Reduced DIDS-sensitive chloride conductance in Ae1−/− mouse erythrocytes

Anion Exchangers of Mammalian Cell Membranes

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