# Membrane shape transition control in cellular membrane trafficking phenomena

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $341,670

## Abstract

Membrane shape transition control in cellular membrane trafficking phenomena
Tobias Baumgart, PI
PROJECT SUMMARY
 Dynamic changes in membrane shape are at the heart of cellular membrane trafficking phenomena such
as endocytosis, where intracellular transport vehicles form from plasma membrane invaginations. Progress in
research aimed to mechanistically understand endocytosis has been challenged in part by the existence of
several different endocytic pathways. Clathrin-mediated endocytosis is the best characterized internalization
route – it is responsible for the bulk of endocytic trafficking and is comparatively slow. Alternative pathways
enable cells to rapidly respond to signals at the plasma membrane. A recently discovered pathway achieves
fast responsiveness trough the assembly of transient complexes containing endophilin: a BAR domain protein,
and lamellipodin: a multivalent adaptor protein. In this process termed fast endophilin-mediated endocytosis
(FEME), dynamic complexes are formed through multivalent interactions that are stabilized through
interactions with activated receptors, including members of the receptor tyrosine kinase (RTK), and G-protein
coupled receptor (GPCR) classes. Whereas RTKs interact with endophilin only indirectly, involving additional
adaptor proteins, several GPCRs show direct endophilin interactions, mediated by the receptors’ third
intracellular loop (TIL), which becomes exposed upon receptor engagement by ligand. The combination of
GPCR, endophilin, and lamellipodin, therefore represents an ideal system upon which to build an in-depth
biophysical description of the mechanisms behind receptor internalization.
 Our goal is to investigate such mechanisms with the help of model membranes consisting primarily of giant
unilamellar vesicles (GUVs) which allow the study of membrane shape transitions under precise control of
membrane tension, using techniques that we have developed and refined over the course of this project.
 A second challenge towards a complete mechanistic understanding of plasma membrane internalization
transitions is that membrane shape changes involve interactions in several different layers, all of which must
receive due attention. We address this challenge in three aims that each are focused on a single layer, roughly
defined by their distance from the membrane. The first aim furthers the understanding of mechanisms that
determine the spontaneous bending preference (spontaneous curvature) of the bilayer itself – a prerequisite for
rigorous design of the following two aims. A second aim asks how TIL binding modulates endophilin function
on the membrane. The third aim considers multivalent interactions occurring distal from the membrane.
Specifically, we will test the hypothesis that multivalent interactions involving endophilin’s SH3 domain and
lamellipodin’s proline-rich domains, could give rise to critical density fluctuations near a protein-protein
(demixing) phase transition, that couples wi...

## Key facts

- **NIH application ID:** 10477946
- **Project number:** 5R01GM097552-12
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Tobias Baumgart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $341,670
- **Award type:** 5
- **Project period:** 2011-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477946

## Citation

> US National Institutes of Health, RePORTER application 10477946, Membrane shape transition control in cellular membrane trafficking phenomena (5R01GM097552-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10477946. Licensed CC0.

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