# Molecular Regulation of Exocytosis

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $336,978

## Abstract

Project Summary
Exocytosis is important for the survival, growth and functions of all eukaryotic cells, and is
centrally involved in many physiological processes ranging from neurotransmission to
organogenesis. Exocytosis is mediated by transport, docking and fusion of secretory vesicles
carrying cargos to the plasma membrane. The exocyst is an evolutionarily conserved octameric
protein complex essential for exocytosis. Malfunction of the exocyst has been linked to diabetes,
Autosomal Polycystic Kidney Diseases and cancer. We have recently solved the structure of the
fully assembled exocyst complex by cryo-electron microscopy and identified two four-helix
bundles, termed “CorEx”, that potentially mediate the core assembly of the exocyst complex. In
this proposal, we will first study the molecular interactions and high-resolution structure of the
CorEx taking a multipronged approach that combines biochemistry, biophysics, crystallography,
and microscopic imaging. We will also determine the function of the exocyst complex in
SNARE assembly and membrane fusion using in vitro reconstituted liposome systems. Finally, we
will examine the functional implication of a newly identified interaction between the exocyst and
EHD proteins, which function in the generation of tubular vesicular carriers from the endosomal
compartments. We will further examine the regulation of the exocyst-EHD interaction by RalA,
a small GTPase that controls endosomal recycling to the plasma membrane in response to
growth factor signaling. Our work will not only help elucidate the mechanisms of exocytosis
at the molecular level, but also shed light to a number of diseases such as diabetes and cancer.

## Key facts

- **NIH application ID:** 10004662
- **Project number:** 5R01GM111128-07
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** WEI GUO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,978
- **Award type:** 5
- **Project period:** 2014-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004662

## Citation

> US National Institutes of Health, RePORTER application 10004662, Molecular Regulation of Exocytosis (5R01GM111128-07). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10004662. Licensed CC0.

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