# Proximal tubule endocytosis in normal and nephrotic kidneys

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $452,130

## Abstract

Abstract
A major function of cells linking the proximal tubule (PT) of the kidney is to recover proteins that escape
the glomerular filtration barrier to maintain a protein-free urine. Apical endocytosis in PT cells is acutely
modulated by changes in fluid shear stress (FSS), presumably to enable efficient protein uptake over
normal variations in glomerular filtration rate (GFR). The large multiligand receptors megalin and
cubilin/amnionless (CUBAM) are expressed at the apical surface of PT cells and mediate the
internalization of >50 different plasma proteins. Despite the critical role of the PT in reclaiming proteins
from the ultrafiltrate, we know surprisingly little about how the cells lining this segment accommodate
variations in filtered load to maintain a protein free urine. Fundamental issues, including how the robust
PT apical endocytic pathway is developed and maintained, the individual role of megalin and CUBAM
receptors in albumin uptake, how PT cells respond to changes in albumin concentration or tubular flow
rate, and the fate of internalized albumin remain controversial. We have developed a new cell culture
model that recapitulates morphological and functional features of PT cells in vivo necessary for efficient
and rapidly modulated apical endocytosis of albumin. We will use these cells in conjunction with studies
in mouse models to address the following questions about how PT cells respond to normal and
pathologic variations in flow and filtered protein load: 1) How do PT cells develop and maintain a high
capacity apical endocytic pathway? 2) How do megalin and CUBAM contribute to albumin uptake under
normal and nephrotic conditions? 3) How does the PT respond endocytically to acute changes in GFR?
and 4) How does endocytosis contribute to cytotoxic responses of PT cells during albumin overload?

## Key facts

- **NIH application ID:** 10132740
- **Project number:** 5R01DK118726-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Ora A Weisz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $452,130
- **Award type:** 5
- **Project period:** 2019-04-16 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132740

## Citation

> US National Institutes of Health, RePORTER application 10132740, Proximal tubule endocytosis in normal and nephrotic kidneys (5R01DK118726-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10132740. Licensed CC0.

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