IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubuleCitation formats

  • External authors:
  • Francesca Oltrabella
  • Anthony Jackson-Crawford
  • Guanhua Yan
  • Sarah Rixham
  • Tobias Starborg

Standard

IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubule. / Oltrabella, Francesca; Jackson-Crawford, Anthony ; Yan, Guanhua; Rixham, Sarah; Starborg, Tobias; Lowe, Martin.

In: Human Molecular Genetics, 14.10.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

Oltrabella, F, Jackson-Crawford, A, Yan, G, Rixham, S, Starborg, T & Lowe, M 2021, 'IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubule', Human Molecular Genetics.

APA

Oltrabella, F., Jackson-Crawford, A., Yan, G., Rixham, S., Starborg, T., & Lowe, M. (Accepted/In press). IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubule. Human Molecular Genetics.

Vancouver

Oltrabella F, Jackson-Crawford A, Yan G, Rixham S, Starborg T, Lowe M. IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubule. Human Molecular Genetics. 2021 Oct 14.

Author

Oltrabella, Francesca ; Jackson-Crawford, Anthony ; Yan, Guanhua ; Rixham, Sarah ; Starborg, Tobias ; Lowe, Martin. / IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubule. In: Human Molecular Genetics. 2021.

Bibtex

@article{1b120c53fd3545dcb879947f93c821e8,
title = "IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubule",
abstract = "Endocytosis is a fundamentally important process through which material is internalized into cells from the extracellular environment. In the renal proximal tubule, endocytosis of the abundant scavenger receptor megalin and its co-receptor cubilin play a vital role in retrieving low molecular weight proteins from the renal filtrate. Although we know much about megalin and its ligands, the machinery and mechanisms by which the receptor is trafficked through the endosomal system remain poorly defined. In this study, we show that Ipip27A, an interacting partner of the Lowe syndrome protein OCRL, is required for endocytic traffic of megalin within the proximal renal tubule of zebrafish larvae. Knockout of Ipip27A phenocopies the endocytic phenotype seen upon loss of OCRL, with a deficit in uptake of both fluid-phase and protein cargo, which is accompanied by a reduction in megalin abundance and altered endosome morphology. Rescue and co-depletion experiments indicate that Ipip27A functions together with OCRL to support proximal tubule endocytosis. The results therefore identify Ipip27A as a new player in endocytic traffic in the proximal tubule in vivo and support the view that defective endocytosis underlies the renal tubulopathy in Lowe syndrome and Dent-2 disease.",
author = "Francesca Oltrabella and Anthony Jackson-Crawford and Guanhua Yan and Sarah Rixham and Tobias Starborg and Martin Lowe",
year = "2021",
month = oct,
day = "14",
language = "English",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - IPIP27A cooperates with OCRL to support endocytic traffic in the zebrafish pronephric tubule

AU - Oltrabella, Francesca

AU - Jackson-Crawford, Anthony

AU - Yan, Guanhua

AU - Rixham, Sarah

AU - Starborg, Tobias

AU - Lowe, Martin

PY - 2021/10/14

Y1 - 2021/10/14

N2 - Endocytosis is a fundamentally important process through which material is internalized into cells from the extracellular environment. In the renal proximal tubule, endocytosis of the abundant scavenger receptor megalin and its co-receptor cubilin play a vital role in retrieving low molecular weight proteins from the renal filtrate. Although we know much about megalin and its ligands, the machinery and mechanisms by which the receptor is trafficked through the endosomal system remain poorly defined. In this study, we show that Ipip27A, an interacting partner of the Lowe syndrome protein OCRL, is required for endocytic traffic of megalin within the proximal renal tubule of zebrafish larvae. Knockout of Ipip27A phenocopies the endocytic phenotype seen upon loss of OCRL, with a deficit in uptake of both fluid-phase and protein cargo, which is accompanied by a reduction in megalin abundance and altered endosome morphology. Rescue and co-depletion experiments indicate that Ipip27A functions together with OCRL to support proximal tubule endocytosis. The results therefore identify Ipip27A as a new player in endocytic traffic in the proximal tubule in vivo and support the view that defective endocytosis underlies the renal tubulopathy in Lowe syndrome and Dent-2 disease.

AB - Endocytosis is a fundamentally important process through which material is internalized into cells from the extracellular environment. In the renal proximal tubule, endocytosis of the abundant scavenger receptor megalin and its co-receptor cubilin play a vital role in retrieving low molecular weight proteins from the renal filtrate. Although we know much about megalin and its ligands, the machinery and mechanisms by which the receptor is trafficked through the endosomal system remain poorly defined. In this study, we show that Ipip27A, an interacting partner of the Lowe syndrome protein OCRL, is required for endocytic traffic of megalin within the proximal renal tubule of zebrafish larvae. Knockout of Ipip27A phenocopies the endocytic phenotype seen upon loss of OCRL, with a deficit in uptake of both fluid-phase and protein cargo, which is accompanied by a reduction in megalin abundance and altered endosome morphology. Rescue and co-depletion experiments indicate that Ipip27A functions together with OCRL to support proximal tubule endocytosis. The results therefore identify Ipip27A as a new player in endocytic traffic in the proximal tubule in vivo and support the view that defective endocytosis underlies the renal tubulopathy in Lowe syndrome and Dent-2 disease.

M3 - Article

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

ER -