# Endocytic dynamics and surface emergent property of leukocyte Integrins

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $482,241

## Abstract

Project Summary
Regulation and sorting of leukocyte integrins are fundamental questions in cell adhesion and polarity that has
great implication for various inflammatory and autoimmune diseases, but it has been poorly studied compared
to cell adhesion receptors in fibroblast cells. We propose to investigate the sorting of leukocyte integrins
and tetraspanin proteins that play critical role in immune cell adhesion and migration. We propose its
dynamic sorting depends on a novel F-BAR-dependent mechanism that not only depends on curvature,
but on a specific range of shallow curvature. We also propose that this mechanism is governing the
mesoscale pattern these receptors are assembled, including propagating gradients and cortical
oscillations, which link trafficking events to cell polarity. Specifically, in Aim 1, we plan to characterize
surface expression and dynamics of these potential transmembrane protein cargos including integrin αMβ2
and CD81 after systematically identify and validate membrane cargos for the endocytic pathway mediated by
F-BAR protein FBP17 and CIP4 using nonbiased proteomic approach. In Aim 2, we aim to isolate the factor
of membrane curvature and tension using well-defined in vitro systems and to determine their effects on F-
BAR membrane binding and tubulation. We will employ a nanobar-based supported bilayer system to critically
evaluate if F-BAR protein senses curvature. We will also test the hypothesis that membrane tubulation may
require lipid sorting and active membrane mechanics. These experiments will provide a quantitative
biophysical understanding of how F-BAR proteins tubulate membranes without the hydrophobic insertion
mechanisms commonly used by other BAR proteins. In Aim 3, we will dissect the functional consequences of
the altered trafficking by examining spontaneous migration or migration under confinement. In particular, we
will investigate the mechanism for polarized membrane receptor gradient formation. Collectively, combining
advanced single cell imaging, genome-editing, proteomics, and in vitro reconstitution, the proposed research
will shed key insights into the regulation and function of leukocyte integrins through sophisticated coordination
and regulatory mechanisms operating at multiple spatial and temporal scales that have not yet been
investigated.

## Key facts

- **NIH application ID:** 10716618
- **Project number:** 1R01GM151344-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Min Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $482,241
- **Award type:** 1
- **Project period:** 2023-09-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10716618

## Citation

> US National Institutes of Health, RePORTER application 10716618, Endocytic dynamics and surface emergent property of leukocyte Integrins (1R01GM151344-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10716618. Licensed CC0.

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