Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.

<h4>Background</h4>A growing number of proteins, including ion transporters, have been shown to interact with Cystic Fibrosis Transmembrane conductance Regulator (CFTR). CFTR is an epithelial chloride channel that is involved in Cystic Fibrosis (CF) when mutated; thus a better knowledge...

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Autores principales:	Naziha Bakouh, Baya Chérif-Zahar, Philippe Hulin, Dominique Prié, Gérard Friedlander, Aleksander Edelman, Gabrielle Planelles
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0fa24138658146a4b51424fe009f353a
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spelling	oai:doaj.org-article:0fa24138658146a4b51424fe009f353a2021-11-18T07:22:14ZFunctional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.1932-620310.1371/journal.pone.0034879https://doaj.org/article/0fa24138658146a4b51424fe009f353a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22514683/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>A growing number of proteins, including ion transporters, have been shown to interact with Cystic Fibrosis Transmembrane conductance Regulator (CFTR). CFTR is an epithelial chloride channel that is involved in Cystic Fibrosis (CF) when mutated; thus a better knowledge of its functional interactome may help to understand the pathophysiology of this complex disease. In the present study, we investigated if CFTR and the sodium-phosphate co-transporter type 2a (NPT2a) functionally interact after heterologous expression of both proteins in Xenopus laevis oocytes.<h4>Methodology/findings</h4>NPT2a was expressed alone or in combination with CFTR in X. laevis oocytes. Using the two-electrode voltage-clamp technique, the inorganic phosphate-induced current (IPi) was measured and taken as an index of NPT2a activity. The maximal IPi for NPT2a substrates was reduced when CFTR was co-expressed with NPT2a, suggesting a decrease in its expression at the oolemna. This was consistent with Western blot analysis showing reduced NPT2a plasma membrane expression in oocytes co-expressing both proteins, whereas NPT2a protein level in total cell lysate was the same in NPT2a- and NPT2a+CFTR-oocytes. In NPT2a+CFTR- but not in NPT2a-oocytes, IPi and NPT2a surface expression were increased upon PKA stimulation, whereas stimulation of Exchange Protein directly Activated by cAMP (EPAC) had no effect. When NPT2a-oocytes were injected with NEG2, a short amino-acid sequence from the CFTR regulatory domain that regulates PKA-dependent CFTR trafficking to the plasma membrane, IPi values and NPT2a membrane expression were diminished, and could be enhanced by PKA stimulation, thereby mimicking the effects of CFTR co-expression.<h4>Conclusion/perspectives</h4>We conclude that when both CFTR and NPT2a are expressed in X. laevis oocytes, CFTR confers to NPT2a a cAMPi-dependent trafficking to the membrane. This functional interaction raises the hypothesis that CFTR may play a role in phosphate homeostasis.Naziha BakouhBaya Chérif-ZaharPhilippe HulinDominique PriéGérard FriedlanderAleksander EdelmanGabrielle PlanellesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34879 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Naziha Bakouh Baya Chérif-Zahar Philippe Hulin Dominique Prié Gérard Friedlander Aleksander Edelman Gabrielle Planelles Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.
description	<h4>Background</h4>A growing number of proteins, including ion transporters, have been shown to interact with Cystic Fibrosis Transmembrane conductance Regulator (CFTR). CFTR is an epithelial chloride channel that is involved in Cystic Fibrosis (CF) when mutated; thus a better knowledge of its functional interactome may help to understand the pathophysiology of this complex disease. In the present study, we investigated if CFTR and the sodium-phosphate co-transporter type 2a (NPT2a) functionally interact after heterologous expression of both proteins in Xenopus laevis oocytes.<h4>Methodology/findings</h4>NPT2a was expressed alone or in combination with CFTR in X. laevis oocytes. Using the two-electrode voltage-clamp technique, the inorganic phosphate-induced current (IPi) was measured and taken as an index of NPT2a activity. The maximal IPi for NPT2a substrates was reduced when CFTR was co-expressed with NPT2a, suggesting a decrease in its expression at the oolemna. This was consistent with Western blot analysis showing reduced NPT2a plasma membrane expression in oocytes co-expressing both proteins, whereas NPT2a protein level in total cell lysate was the same in NPT2a- and NPT2a+CFTR-oocytes. In NPT2a+CFTR- but not in NPT2a-oocytes, IPi and NPT2a surface expression were increased upon PKA stimulation, whereas stimulation of Exchange Protein directly Activated by cAMP (EPAC) had no effect. When NPT2a-oocytes were injected with NEG2, a short amino-acid sequence from the CFTR regulatory domain that regulates PKA-dependent CFTR trafficking to the plasma membrane, IPi values and NPT2a membrane expression were diminished, and could be enhanced by PKA stimulation, thereby mimicking the effects of CFTR co-expression.<h4>Conclusion/perspectives</h4>We conclude that when both CFTR and NPT2a are expressed in X. laevis oocytes, CFTR confers to NPT2a a cAMPi-dependent trafficking to the membrane. This functional interaction raises the hypothesis that CFTR may play a role in phosphate homeostasis.
format	article
author	Naziha Bakouh Baya Chérif-Zahar Philippe Hulin Dominique Prié Gérard Friedlander Aleksander Edelman Gabrielle Planelles
author_facet	Naziha Bakouh Baya Chérif-Zahar Philippe Hulin Dominique Prié Gérard Friedlander Aleksander Edelman Gabrielle Planelles
author_sort	Naziha Bakouh
title	Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.
title_short	Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.
title_full	Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.
title_fullStr	Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.
title_full_unstemmed	Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.
title_sort	functional interaction between cftr and the sodium-phosphate co-transport type 2a in xenopus laevis oocytes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0fa24138658146a4b51424fe009f353a
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Functional interaction between CFTR and the sodium-phosphate co-transport type 2a in Xenopus laevis oocytes.

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