# Dynamics of Endomembrane Docking and Fusion

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $340,039

## Abstract

Project Summary
Membrane traffic is among the most ancient innovations of eukaryotic cells. It is central to
neurotransmission, immune signaling, and normal development, and disrupted in a wide array of
infectious and degenerative diseases. The fusion of transport vesicles with target membranes is central to
many trafficking processes and employs a core and conserved machinery: three or four SNARE proteins,
the disassembly chaperones Sec17 (α-SNAP) and Sec18 (NSF), and proteins of the SM (Sec1/Munc18)
family. The mechanism of SM protein function is not understood, though several SM proteins are
associated with human infectious disease, neurodegeneration, neutropenia, and diabetes. The overall goal
of this Project is to scrutinize the emerging hypothesis that the biochemical basis of SM function entails not
only SM–SNARE interactions but an elegant network of physical and functional interactions among
SNAREs, SMs, Sec17, and Sec18, operating in tightly coupled assembly and disassembly reactions. Much of
the recent work on SM proteins and Sec17 has been done in vitro. This Project combines powerful in vitro
biochemical approaches with state-of-the-art in vivo structure–function analyses that are currently feasible
only in Saccharomyces cerevisiae. In Aim 1, the mechanisms of SM protein activation and activity are
assessed in vivo and in vitro. In Aim 2, Sec17 interactions with SNAREs, Sec18, and specific SMs are
assessed. In Aim 3, biophysical techniques are applied to elucidate the architecture of SM assembly with
SNAREs and with Sec17. These studies will test general and deep hypotheses about the conserved
mechanisms of SNARE-mediated membrane fusion, with particular emphasis on comparisons between two
different transport steps, and between in vitro results and stringent and quantitative in vivo structure–
function analyses.

## Key facts

- **NIH application ID:** 9893719
- **Project number:** 5R01GM077349-13
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Alexey Jarrell Merz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,039
- **Award type:** 5
- **Project period:** 2006-03-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893719

## Citation

> US National Institutes of Health, RePORTER application 9893719, Dynamics of Endomembrane Docking and Fusion (5R01GM077349-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9893719. Licensed CC0.

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