Characterization of transport mechanisms and determinants critical for Na<sup>+</sup>-dependent P<sub>i</sub> symport of the PiT family paralogs human PiT1 and PiT2

Bøttger, Pernille; Hede, Susanne E.; Grunnet, Morten; Hoyer, B.; Klærke, Dan A.; Pedersen, Lene

doi:10.1152/ajpcell.00015.2006

Cited by 45 publications

(54 citation statements)

References 46 publications

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“…In the absence of Na + , lowering pH from 7.5 to 6.0 induced significant P i uptake in Xenopus oocytes that expressed PiT-2. This finding suggests that H + may also substitute for Na + for this isoform (Bottger, Hede et al 2006;). The increased K 0.5…”

Section: Slc20mentioning

confidence: 92%

“…(Kavanaugh, Miller et al 1994;Bai, Collins et al 2000;Bottger, Hede et al 2006;Ravera, Virkki et al 2007)). A cooperative P i -dependence was reported for PiT-2 expressed in Xenopus oocytes under non-voltage clamped conditions, a finding consistent with this isoform behaving as a functional dimer (Bottger, Hede et al 2006). This finding has yet to be confirmed under voltage-clamp conditions.…”

Section: Slc20mentioning

confidence: 99%

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Phosphate Transport Kinetics and Structure-Function Relationships of SLC34 and SLC20 Proteins

Forster

Hernando

Biber

et al. 2012

Current Topics in Membranes

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Transport of inorganic phosphate (P(i)) is mediated by proteins belonging to two solute carrier families (SLC20 and SLC34). Members of both families transport P(i) using the electrochemical gradient for Na(+). The role of the SLC34 members as essential players in mammalian P(i) homeostasis is well established, whereas that of SLC20 proteins is less well defined. The SLC34 family comprises the following three isoforms that preferentially cotransport divalent P(i) and are expressed in epithelial tissue: the renal NaPi-IIa and NaPi-IIc are responsible for reabsorbing P(i) in the proximal tubule, whereas NaPi-IIb is more ubiquitously expressed, including the small intestine, where it mediates dietary P(i) absorption. The SLC20 family comprises two members (PiT-1, PiT-2) that preferentially cotransport monovalent P(i) and are expressed in epithelial as well as nonepithelial tissue. The transport kinetics of members of both families have been characterized in detail using heterologous expression in Xenopus oocytes. For the electrogenic NaPi-IIa/b, and PiT-1,-2, conventional electrophysiological techniques together with radiotracer methods have been applied, as well as time-resolved fluorometric measurements that allow new insights into local conformational changes of the protein during the cotransport cycle. For the electroneutral NaPi-IIc, conventional tracer uptake and fluorometry have been used to elucidate its transport properties. The 3-D structures of these proteins remain unresolved and structure-function studies have so far concentrated on defining the topology and identifying sites of functional importance. DOI: https://doi.org/10.1016/ B978-0-12-394316-3.00010-7 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-73295 Accepted Version Originally published at: Forster, Ian C; Hernando, Nati; Biber, Jürg; Murer, Heini (2012). Phosphate transport kinetics and structure-function relationships of SLC34 and SLC20 proteins. Current Topics in Membranes, I. OVERVIEWTransport of inorganic phosphate (P i ) is mediated by proteins belonging to 2 solute carrier families (SLC20 and SLC34). Members of both families transport P i using the electrochemical gradient for Na + . Whereas the role of the SLC34 members as essential players in mammalian P i homeostasis is well established, that of SLC20 proteins is less well defined. The SLC34 family comprises the following 3 isoforms that preferentially cotransport divalent P i and are expressed in epithelial tissue: the renal NaPi-IIa and NaPi-IIc are responsible for reabsorbing P i in the proximal tubule, whereas NaPi-IIb is more ubiquitously expressed, including the small intestine, where it mediates dietary P i absorption. The SLC20 family comprises 2 members (PiT-1, PiT-2) that preferentially cotransport monovalent P i and are expressed in epithelial as well as non-epithelial tissue. The transport kinetics of members of both families have been characterized in detail using heterologous expression in Xenop...

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Section: Slc20mentioning

confidence: 92%

Section: Slc20mentioning

confidence: 99%

Phosphate Transport Kinetics and Structure-Function Relationships of SLC34 and SLC20 Proteins

Forster

Hernando

Biber

et al. 2012

Current Topics in Membranes

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“…We have found that VSMCs exhibit both Na-dependent and Naindependent Pi transport components with similar kinetic behavior, but that only the Na-coupled saturable uptake can be explained by the expression of both type III NaPi (NaPi-III) transporters, Pit1 and Pit2. 14 As an article has recently been published regarding the characteristics of Pi transport by Pit1 and Pit2 while preparing this manuscript, 15 this article will focus on the different and novel findings we have found.…”

mentioning

confidence: 98%

Characterization of Phosphate Transport in Rat Vascular Smooth Muscle Cells

Villa‐Bellosta

Bogaert

Levi

et al. 2007

ATVB

115

139

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Objective-Hyperphosphatemia and inorganic phosphate (Pi) transport by vascular smooth muscle cells (VSMCs) have been implicated in the pathogenesis of vascular calcification. The aim of this work has been to characterize Pi transport in VSMCs. Methods and Results-Primary cultures of VSMCs express both high affinity Na-dependent and Na-independent components of Pi transport. Under physiological conditions both transport systems are saturated, show similar activity, and are inhibited by increasing pH. The Na-dependent transport is also weakly inhibited by phosphonoformic acid (PFA) (3.9 mmol/L IC 50 at 0.05 mmol/L Pi). Real-time polymerase chain reaction shows that Pit1 and Pit2 are expressed to the same degree, and no other Pi transporters are significantly expressed. When expressed in Xenopus oocytes they are strictly Na-dependent, with high affinities for Pi, and are inhibited by increasing pH, but only weakly inhibited by PFA. We have used RNA interference to demonstrate that Pit1 and Pit2 are the transporters responsible for Na-dependent Pi transport in VSMCs. Conclusions-Taken

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“…From these and other studies (e.g. (Bai et al, 2000;Bottger et al, 2006;Olah et al, 1994)) it became apparent that SLC20 proteins were functionally distinct from SLC34 proteins. These differences were highlighted in a detailed characterization of PiT-1 transport kinetics .…”

Section: Kineticsmentioning

confidence: 76%

“…Unlike SLC34 proteins that are exclusively Na + drive, for PiT-1, Li + can fully replace Na + as the driving cation, albeit with a significantly reduced transport rate . Furthermore, in the absence of Na + , lowering pH from 7.5 to 6.0 induces significant P i uptake in Xenopus oocytes that expressed PiT-2, which suggest that H + may also substitute for Na + for this isoform (Bottger et al, 2006;Villa-Bellosta et al, 2007). Na + is the first ion to interact followed by a random binding of Na + and P i .…”

Section: Kineticsmentioning

confidence: 99%

Phosphate transporters of the SLC20 and SLC34 families

Forster

Hernando

Biber

et al. 2013

Molecular Aspects of Medicine

180

198

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Transport of inorganic phosphate (Pi) across the plasma membrane is essential for normal cellular function. Members of two families of SLC proteins (SLC20 and SLC34) act as Na(+)-dependent, secondary-active cotransporters to transport Pi across cell membranes. The SLC34 proteins are expressed in specific organs important for Pi homeostasis: NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3) fulfill essential roles in Pi reabsorption in the kidney proximal tubule and NaPi-IIb (SLC34A2) mediates Pi absorption in the gut. The SLC20 proteins, PiT-1 (SLC20A1), PiT-2 (SLC20A2) are expressed ubiquitously in all tissues and although generally considered as "housekeeping" transport proteins, the discovery of tissue-specific activity, regulatory pathways and gene-related pathophysiologies, is redefining their importance. This review summarizes our current knowledge of SLC20 and SLC34 proteins in terms of their basic molecular characteristics, physiological roles, known pathophysiology and pharmacology. AbstractTransport of inorganic phosphate (P i ) across the plasma membrane is essential for normal cellular function. Members of two families of SLC proteins (SLC20 and SLC34) act as Na + -dependent, secondary-active cotransporters to transport P i across cell membranes. The SLC34 proteins are expressed in specific organs important for P i homeostasis: NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3) fulfill essential roles in P i reabsorption in the kidney proximal tubule and NaPi-IIb (SLC34A2) mediates P i absorption in the gut. The SLC20 proteins, PiT-1 (SLC20A1), PiT-2 (SLC20A2) are expressed ubiquitously in all tissues and although generally considered as "housekeeping" transport proteins, the discovery of tissue-specific activity,regulatory pathways and gene-related pathophysiologies, is redefining their importance. This review summarises our current knowledge of SLC20 and SLC34 proteins in terms of their basic molecular characteristics, physiological roles, known pathophysiologies and pharmacology.3

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Characterization of transport mechanisms and determinants critical for Na⁺-dependent P_i symport of the PiT family paralogs human PiT1 and PiT2

Abstract: . Characterization of transport mechanisms and determinants critical for Na ϩ -dependent Pi symport of the PiT family paralogs human PiT1 and PiT2.

Cited by 45 publications

References 46 publications

Phosphate Transport Kinetics and Structure-Function Relationships of SLC34 and SLC20 Proteins

Phosphate Transport Kinetics and Structure-Function Relationships of SLC34 and SLC20 Proteins

Characterization of Phosphate Transport in Rat Vascular Smooth Muscle Cells

Phosphate transporters of the SLC20 and SLC34 families

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Characterization of transport mechanisms and determinants critical for Na+-dependent Pi symport of the PiT family paralogs human PiT1 and PiT2

Abstract: . Characterization of transport mechanisms and determinants critical for Na ϩ -dependent Pi symport of the PiT family paralogs human PiT1 and PiT2.

Cited by 45 publications

References 46 publications

Phosphate Transport Kinetics and Structure-Function Relationships of SLC34 and SLC20 Proteins

Phosphate Transport Kinetics and Structure-Function Relationships of SLC34 and SLC20 Proteins

Characterization of Phosphate Transport in Rat Vascular Smooth Muscle Cells

Phosphate transporters of the SLC20 and SLC34 families

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Product

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Characterization of transport mechanisms and determinants critical for Na⁺-dependent P_i symport of the PiT family paralogs human PiT1 and PiT2