Kidney Tubular Ablation of / Phenocopies Lowe Syndrome Tubulopathy

Overview

Journal J Am Soc Nephrol

Specialty Nephrology

Date 2016 Nov 30

PMID 27895154

Citations 17

Authors

Kazunori Inoue

Daniel M Balkin

Lijuan Liu

Ramiro Nandez

Yumei Wu

Xuefei Tian

Tong Wang

Robert Nussbaum

Pietro De Camilli

Shuta Ishibe

Affiliations

Soon will be listed here.

Abstract

Lowe syndrome and Dent disease are two conditions that result from mutations of the inositol 5-phosphatase oculocerebrorenal syndrome of Lowe (OCRL) and share the feature of impaired kidney proximal tubule function. Genetic ablation of in mice failed to recapitulate the human phenotypes, possibly because of the redundant functions of OCRL and its paralog type 2 inositol polyphosphate-5-phosphatase (INPP5B). Germline knockout of both paralogs in mice results in early embryonic lethality. We report that kidney tubule-specific inactivation of on a global -knockout mouse background resulted in low molecular weight proteinuria, phosphaturia, and acidemia. At the cellular level, we observed a striking impairment of clathrin-dependent and -independent endocytosis in proximal tubules, phenocopying what has been reported for Dent disease caused by mutations in the gene encoding endosomal proton-chloride exchange transporter 5. These results suggest that the functions of OCRL/INPP5B and proton-chloride exchange transporter 5 converge on shared mechanisms, the impairment of which has a dramatic effect on proximal tubule endocytosis.

Citing Articles

WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration.

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WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration.

Coulter A, Cortes V, Theodore C, Cianciolo R, Korstanje R, Campellone K bioRxiv. 2024; .

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The Role of Primary Cilia-Associated Phosphoinositide Signaling in Development.

Chen C, Hu J, Ling K J Dev Biol. 2022; 10(4).

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A 3D Renal Proximal Tubule on Chip Model Phenocopies Lowe Syndrome and Dent II Disease Tubulopathy.

Naik S, Wood A, Ongenaert M, Saidiyan P, Elstak E, Lanz H Int J Mol Sci. 2021; 22(10).

PMID: 34069732 PMC: 8161077. DOI: 10.3390/ijms22105361.

Glomerular podocyte dysfunction in inherited renal tubular disease.

Huang L, Mao J World J Pediatr. 2021; 17(3):227-233.

PMID: 33625696 PMC: 8253710. DOI: 10.1007/s12519-021-00417-0.

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