# Molecular mechanisms of coat assembly and regulation in membrane trafficking pathways

> **NIH NIH R35** · VANDERBILT UNIVERSITY · 2022 · $455,885

## Abstract

Project Summary
The timely delivery of membrane-bound vesicles and tubules bearing transmembrane protein and lipid cargoes
to discrete cellular membranes is fundamental to cell biology and human health. Many proteins associated with
trafficking pathways are linked to serious and crippling human diseases, especially neurological diseases and
disorders. Although many trafficking proteins and some pathways are well characterized, we still do not
understand other trafficking pathways that we infer must exist between membranes. This constitutes an
enormous gap in our understanding of fundamental cell biology. Our goal is to elucidate the molecular
structures and functions of important coat protein complexes that initiate trafficking pathways by forming coats
around vesicles or tubules. Coat proteins recognize and package relevant cargoes, and they promote efficient
assembly of additional required protein components, like accessory proteins and SNAREs. Clathrin coats have
long served as an important paradigm, but increasing evidence demonstrates how other coats use distinct
mechanisms. We investigate the retromer and Assembly Polypeptide (AP) family of coat complexes (COPI,
AP-4, AP-5) by using a variety of tools to ascertain molecular mechanisms of coat assembly and regulation.
Biochemical approaches allow us to identify and test new interactions in coat complexes, including how
accessory and regulatory proteins drive function. Integrated structural methods including X-ray crystallography,
cryo-electron microscopy (cryo-EM), and cryo-electron tomography (cryo-ET) provide detailed evidence for
how coats interact with key partners and allow us to generate specific hypotheses to test function. Biophysical
techniques enable us to quantify binding affinities and to probe interfaces identified in structural models. With
collaborators, we use molecular data to design experiments in cultured cell lines or in model organisms to
explore how protein-protein interactions drive phenotypes at the cellular or organismal levels. Ultimately, we
hope to gain a molecular understanding of how coats assemble at distinct membranes to drive different
trafficking pathways. We anticipate this work will reveal new mechanisms of coat assembly and regulation and
will provide fundamental insights into the protein networks that underlie key cellular events on membranes.

## Key facts

- **NIH application ID:** 10405921
- **Project number:** 2R35GM119525-06
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Lauren Parker Jackson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $455,885
- **Award type:** 2
- **Project period:** 2016-09-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405921

## Citation

> US National Institutes of Health, RePORTER application 10405921, Molecular mechanisms of coat assembly and regulation in membrane trafficking pathways (2R35GM119525-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10405921. Licensed CC0.

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