# Role of Clathrin Mediated Endocytosis in Podocyte Biology

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $376,875

## Abstract

Project Summary
Chronic kidney disease (CKD) often leads to irreversible deterioration of kidney function that
often progresses to End Stage Kidney Disease (ESKD). CKD has emerged as a serious public
health issue and data obtained from the USRDS reveals that the number 20 million patients in
the United States suffer from CKD. As glomerular diseases secondary to podocyte dysfunction
account for greater than 80% of all CKD, an intensive molecular and genetic approach to
identify mechanisms for podocyte development, maintenance and repair may provide new
therapeutic targets Recent evidence suggests an important role of clathrin mediated
endocytosis orchestrating podocyte function. Using genetic mouse models, we have discovered
proteins involved in mediating clathrin mediated endocytosis such as synaptojanin 1, dynamin,
and endophilin, are indispensible for maintaining a normally functioning filtration barrier. We
have further extended our findings that GAK, a protein important for uncoating clathrin, is
equally important. To probe the mechanism, a microarray analysis on enriched glomeruli was
performed revealing a plethora of actin-regulated genes containing a serum response element
regulated by the serum response factor. We have also taken advantage of human kidney
biopsies from patients with focal segmental glomerulosclerosis (FSGS), which also
demonstrated reduced GAK expression and increased serum response factor expression.
Therefore In Aim 1, we will define the fundamental mechanisms on how loss of GAK contributes
to podocyte dysfunction through abnormal actin dynamics mediated by serum response factor.
In Aim 2, we will characterize the role of GAK's C-terminus to stabilize podocyte function and
further investigate the link between endocytosis and actin in podocytes. Our mouse models of
disease with human FSGS biopsy findings provide impetus to further define the role of clathrin-
mediated endocytosis in the formation and maintenance an intact glomerular filtration barrier.

## Key facts

- **NIH application ID:** 10225537
- **Project number:** 5R01DK093629-09
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Shuta Ishibe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $376,875
- **Award type:** 5
- **Project period:** 2012-09-27 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225537

## Citation

> US National Institutes of Health, RePORTER application 10225537, Role of Clathrin Mediated Endocytosis in Podocyte Biology (5R01DK093629-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10225537. Licensed CC0.

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