GABARAP deficiency modulates expression of NaPi-IIa in renal brush-border membranes

Reining, Sonja C; Gisler, Serge M; Fuster, Daniel Guido; Moe, Orson W; O'Sullivan, Gregory A; Betz, Heinrich; Biber, Jürg; Murer, Heini; Hernando, Nati (2009). GABARAP deficiency modulates expression of NaPi-IIa in renal brush-border membranes. American journal of physiology - renal physiology, 296(5), F1118-28. Bethesda, Md.: American Physiological Society 10.1152/ajprenal.90492.2008

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Renal reabsorption of inorganic phosphate (P(i)) is mainly mediated by the Na(+)-dependent P(i)-cotransporter NaPi-IIa that is expressed in the brush-border membrane (BBM) of renal proximal tubules. Regulation and apical expression of NaPi-IIa are known to depend on a network of interacting proteins. Most of the interacting partners identified so far associate with the COOH-terminal PDZ-binding motif (TRL) of NaPi-IIa. In this study GABA(A) receptor-associated protein (GABARAP) was identified as a novel interacting partner of NaPi-IIa applying a membrane yeast-two-hybrid system (MYTH 2.0) to screen a mouse kidney library with the TRL-truncated cotransporter as bait. GABARAP mRNA and protein are present in renal tubules, and the interaction of NaPi-IIa and GABARAP was confirmed by using glutathione S-transferase pulldowns from BBM and coimmunoprecipitations from transfected HEK293 cells. Amino acids 36-68 of GABARAP were identified as the determinant for the described interaction. The in vivo effects of this interaction were studied in a murine model. GABARAP(-/-) mice have reduced urinary excretion of P(i), higher Na(+)-dependent (32)P(i) uptake in BBM vesicles, and increased expression of NaPi-IIa in renal BBM compared with GABARAP(+/+) mice. The expression of Na(+)/H(+) exchanger regulatory factor (NHERF)1, an important scaffold for the apical expression of NaPi-IIa, is also increased in GABARAP(-/-) mice. The absence of GABARAP does not interfere with the regulation of the cotransporter by either parathyroid hormone or acute changes of dietary P(i) content.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension

UniBE Contributor:

Fuster, Daniel Guido

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0363-6127

Publisher:

American Physiological Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:14

Last Modified:

19 Jan 2016 15:48

Publisher DOI:

10.1152/ajprenal.90492.2008

PubMed ID:

19225049

Web of Science ID:

000265529600021

BORIS DOI:

10.7892/boris.32701

URI:

https://boris.unibe.ch/id/eprint/32701 (FactScience: 198001)

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