# Membrane communication: the foundation of renal epithelial structure

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $497,973

## Abstract

Each of the cell types of the nephron possesses segment-specific structural and biochemical specializations that
both reflect and define its physiological properties. Nephron transport requires the asymmetric apportioning of
ion transport proteins among the apical and basolateral plasma membrane domains of tubule epithelial cells.
Polarized plasma membrane domains are a prerequisite for normal renal function, and their perturbation
contributes to a variety of pathologies. To accommodate transport proteins, renal epithelial cells sculpt their
plasma membranes into organized domains whose designs are exquisitely well suited to their physiological
occupations. Furthermore, the organelles that populate renal epithelial cells participate in contacts and
communication pathways through which they help to meet the metabolic, structural and biosynthetic demands
imposed by renal transport. Elucidating the network of interactions that generate and maintain renal epithelial
cell structure is central to understanding renal physiology. The past several years have seen the emergence of
completely new understandings of the mechanisms through which the membranes of subcellular organelles
communicate with one another and with the molecules that govern vesicular transport. A wide variety of
membrane contact sites have been identified that not only tether subcellular structures to one another but also
mediate inter-organelle communication and exchange. The inositol phospholipid compositions of organelle
membranes and of sub-domains of the plasmalemma help to establish the identities of these membranes and
define their interactions with the cellular sorting and trafficking machinery. While the roles of these contact sites
and of the segregated distributions of inositol phospholipids has been established extensively in cultured cell
systems, very little is known of their physiologic functions in epithelial cells that line renal tubules in situ. We
hypothesize that the unique architecture of renal epithelial cells is predicated upon contact-mediated and inositol
phospholipid-mediated communication among subcellular compartments. The studies outlined in the present
proposal will explore the mechanisms through which renal tubule epithelial cell plasma membranes acquire and
modulate some of their characteristic adaptations. The hypothesis that motivates these studies is that renal
epithelial cell structure and function are predicated upon networks of protein-protein interactions and signaling
pathways that collaborate with one another to communicate and respond to environmental cues. To explore this
hypothesis and its implications in depth we will: 1) Define the nature, localization and ontogeny of membrane
contact sites in renal epithelial cells; 2) Define the biochemical compositions of contact sites in the kidney and
the roles of contact sites in renal development and function; and 3) Define the distributions of inositol
phospholipids in renal epithelial cells in vivo ...

## Key facts

- **NIH application ID:** 10436282
- **Project number:** 5R01DK072614-31
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Michael J. Caplan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $497,973
- **Award type:** 5
- **Project period:** 1989-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436282

## Citation

> US National Institutes of Health, RePORTER application 10436282, Membrane communication: the foundation of renal epithelial structure (5R01DK072614-31). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10436282. Licensed CC0.

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