Primary structure and functional expression of the Na/Ca,K-exchanger from bovine rod photoreceptors.

Reiländer, Helmut; Achilles, Anita; Friedel, Ute; Maul, Gabi; Lottspeich, Friedrich; Cook, Neil J.

doi:10.1002/j.1460-2075.1992.tb05219.x

Cited by 190 publications

(125 citation statements)

References 45 publications

(31 reference statements)

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“…Comparison of the deduced amino acid sequence of this novel gene (Figs. 1 and 2) revealed a significant level of similarity to the two known members of the K ϩ -dependent Na ϩ /Ca 2ϩ exchanger family as follows: NCKX1, first identified in retinal rod outer segments (19), and NCKX2, originally identified in rat brain and then in chicken and human retinal cone and ganglion cells (28,29). Thus, the novel gene presented here encodes the third member of the K ϩ -dependent Na ϩ /Ca 2ϩ exchanger gene family and will be referred to as NCKX3 (gene SLC24A3).…”

Section: Identification In Human Brain and Skeletal Muscle Of A Novelmentioning

confidence: 99%

“…NCKX1 was first cloned from bovine retina (19) and, more recently, from other species including dolphin, rat, buffalo, and man (20 -22). This protein 1 The abbreviations used are: NCX, Na ϩ /Ca 2ϩ exchanger; EST, expressed sequence tags; kb, kilobase pair; MOPS, 3-(N-morpholino)propane-sulfonic acid; NCKX, Na ϩ /Ca 2ϩ ϩ K ϩ exchanger; PCR, polymerase chain reaction; RT-PCR, reverse transcription-coupled polymerase chain reaction.…”

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confidence: 99%

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Molecular Cloning of a Third Member of the Potassium-dependent Sodium-Calcium Exchanger Gene Family,NCKX3

Kraev

Lytton

2001

Journal of Biological Chemistry

116

143

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We describe here the identification and characterization of a novel member of the family of K ؉ -dependent Na ؉ /Ca 2؉ exchangers, NCKX3 (gene SLC24A3). Human NCKX3 encodes a protein of 644 amino acids that displayed a high level of sequence identity to the other family members, rod NCKX1 and cone/neuronal NCKX2, in the hydrophobic regions surrounding the "␣ -repeat" sequences thought to form the ion-binding pocket for transport. Outside of these regions NCKX3 showed no significant identity to other known proteins. As anticipated from this sequence similarity, NCKX3 displayed K ؉ -dependent Na ؉ /Ca 2؉ exchanger activity when assayed in heterologous expression systems, using digital imaging of fura-2 fluorescence, electrophysiology, or radioactive 45 Ca 2؉ uptake. The N-terminal region of NCKX3, although not essential for expression, increased functional activity at least 10-fold and may represent a cleavable signal sequence. NCKX3 transcripts were most abundant in brain, with highest levels found in selected thalamic nuclei, in hippocampal CA1 neurons, and in layer IV of the cerebral cortex. Many other tissues also expressed NCKX3 at lower levels, especially aorta, uterus, and intestine, which are rich in smooth muscle. The discovery of NCKX3 thus expands the K ؉ -dependent Na ؉ /Ca 2؉ exchanger family and suggests this class of transporter has a more widespread role in cellular Ca 2؉ handling than previously appreciated.

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Section: Identification In Human Brain and Skeletal Muscle Of A Novelmentioning

confidence: 99%

mentioning

confidence: 99%

Molecular Cloning of a Third Member of the Potassium-dependent Sodium-Calcium Exchanger Gene Family,NCKX3

Kraev

Lytton

2001

Journal of Biological Chemistry

116

143

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“…NCX1 is predominantly expressed in the heart, brain, and kidney, although it is also present in a broad variety of cell types, whereas NCX2 and 3 expression is limited to brain and skeletal muscle (38,42,43). NCKX1 is exclusively expressed in retinal rod outer segments, whereas NCKX2 is expressed in brain and cone photoreceptors (47,48,59). NCKX3 and 4 display a broader pattern of tissue expression, although they are also prominently expressed in the brain (31,36,39).…”

Section: K + -Dependent and Independent Na + /Ca 2+ Exchangersmentioning

confidence: 99%

“…The first K + -dependent Na + /Ca 2+ exchanger to be identified by molecular cloning was NCKX1 from bovine rod photoreceptors (48). Northern blotting and in situ hybridization have demonstrated that the mRNA encoding for this exchanger is found almost exclusively in rod photoreceptors (39).…”

Section: Localizationmentioning

confidence: 99%

K⁺-Dependent Na⁺/Ca²⁺Exchangers: Key Contributors to Ca²⁺Signaling

Visser

Lytton

2007

Physiology

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Ca 2+ acts as a ubiquitous second messenger to control a wide variety of physiological processes by relaying information within mammalian cells (6). For example, Ca 2+ signals trigger fertilization, control development and differentiation, coordinate cellular functions, and even play roles in cell death. The large variety of functional effects are dictated by the spatial and temporal nature of the Ca 2+ signals and by the cellular context in which they occur, that is, the tissue and cell-specific complement of Ca 2+ influx/efflux pathways and downstream targets determine the final outcome. Cytosolic Ca 2+ influx typically occurs when Ca 2+ channels localized to the plasma or endoplasmic reticular membranes open in response to various stimuli such as membrane depolarization or ligand binding (5). Ca 2+ can be subsequently removed from the cytosol by various mechanisms: sarco/endoplasmic reticulum Ca 2+ ATPases (SERCA) and plasma membrane Ca 2+ ATPases (PMCA) utilize the energy from ATP hydrolysis to pump Ca 2+ into the endoplasmic reticulum or outside the cell, respectively, and Na + /Ca 2+ exchangers extrude cytosolic Ca 2+ in exchange for extracellular Na + . In certain cellular contexts, such as localized signals in the dendritic spines of neurons, Ca 2+ flux across the plasma membrane predominates over that from intracellular stores (2, 49). In such cases, PMCA proteins control the resting Ca 2+ concentrations because of their high-affinity/lowcapacity transport properties, whereas Na + /Ca 2+ exchangers display low-affinity/high-capacity transport properties that are ideally suited for cytosolic clearance when Ca 2+ is elevated following a signaling event. Detailed knowledge of the physiological and biochemical properties of calcium channels and transporters is critical to understanding the mechanisms of Ca 2+ signaling in various cellular contexts. This review will focus on recent progress in the understanding of the physiology, function, structure, and regulation of the recently identified family of K + -dependent Na + /Ca 2+ exchangers. K + -Dependent and Independent Na + /Ca 2+ ExchangersThere are two families of Na + /Ca 2+ exchangers in mammalian cells: those that are K + -dependent (NCKX) and those that are K + -independent (NCX). Physiologically, NCX proteins function by extruding cytosolic Ca 2+ in exchange for extracellular Na + ions, whereas NCKX proteins extrude cytosolic Ca 2+ and K + in exchange for Na + ions, which in both cases is referred to as forward mode exchange. In conditions of altered ion gradients and membrane potential, these exchangers can also mediate Ca 2+ entry or so-called reverse mode operation. Three NCX and five NCKX isoforms have been identified by molecular cloning. NCX1 is predominantly expressed in the heart, brain, and kidney, although it is also present in a broad variety of cell types, whereas NCX2 and 3 expression is limited to brain and skeletal muscle (38,42,43). NCKX1 is exclusively expressed in retinal rod outer segments, whereas NCKX2 is expressed in brain and c...

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“…Cloning of bovine RodX (bRodX) 1 was reported by Reilaender et al (2), and the authors suggested that, similar to the cardiac exchanger, the N terminus may function as a cleaved signal sequence. If, in fact, the first 65 aa constitute a cleaved signal sequence, the large N-terminal hydrophilic domain would not be anchored to the membrane by a preceding transmembrane segment.…”

mentioning

confidence: 98%

The Retinal Rod Na+/Ca2+,K+Exchanger Contains a Noncleaved Signal Sequence Required for Translocation of the N Terminus

McKiernan

Friedlander

1999

Journal of Biological Chemistry

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The retinal rod Na ؉ /Ca 2؉ ,K ؉ exchanger (RodX) is a polytopic membrane protein found in photoreceptor outer segments where it is the principal extruder of Ca 2؉ ions during light adaptation. We have examined the role of the N-terminal 65 amino acids in targeting, translocation, and integration of the RodX using an in vitro translation/translocation system. cDNAs encoding human RodX and bovine RodX through the first transmembrane domain were correctly targeted and integrated into microsomal membranes; deletion of the Nterminal 65 amino acids (aa) resulted in a translation product that was not targeted or integrated. Deletion of the first 65 aa had no effect on membrane targeting of full-length RodX, but the N-terminal hydrophilic domain no longer translocated. Chimeric constructs encoding the first 65 aa of bovine RodX fused to globin were translocated across microsomal membranes, demonstrating that the sequence could function heterologously. Studies of fresh bovine retinal extracts demonstrated that the first 65 aa are present in the native protein. These data demonstrate that the first 65 aa of RodX constitute an uncleaved signal sequence required for the efficient membrane targeting and proper membrane integration of RodX.

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Primary structure and functional expression of the Na/Ca,K-exchanger from bovine rod photoreceptors.

Cited by 190 publications

References 45 publications

Molecular Cloning of a Third Member of the Potassium-dependent Sodium-Calcium Exchanger Gene Family,NCKX3

Molecular Cloning of a Third Member of the Potassium-dependent Sodium-Calcium Exchanger Gene Family,NCKX3

K⁺-Dependent Na⁺/Ca²⁺Exchangers: Key Contributors to Ca²⁺Signaling

The Retinal Rod Na+/Ca2+,K+Exchanger Contains a Noncleaved Signal Sequence Required for Translocation of the N Terminus

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Primary structure and functional expression of the Na/Ca,K-exchanger from bovine rod photoreceptors.

Cited by 190 publications

References 45 publications

Molecular Cloning of a Third Member of the Potassium-dependent Sodium-Calcium Exchanger Gene Family,NCKX3

Molecular Cloning of a Third Member of the Potassium-dependent Sodium-Calcium Exchanger Gene Family,NCKX3

K+-Dependent Na+/Ca2+Exchangers: Key Contributors to Ca2+Signaling

The Retinal Rod Na+/Ca2+,K+Exchanger Contains a Noncleaved Signal Sequence Required for Translocation of the N Terminus

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K⁺-Dependent Na⁺/Ca²⁺Exchangers: Key Contributors to Ca²⁺Signaling