# Coordination of membrane traffic through rab GEF and GAP cascades

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $387,500

## Abstract

Project Summary
Rabs constitute the largest branch of the Ras GTPase superfamily, with ten members in yeast and more then
60 in mammalian cells. They serve as key nodes in the regulation of membrane traffic, each typically
controlling several different aspects of a specific stage of membrane traffic by recruiting diverse effector
proteins such as cytoskeletal motors, vesicle tethering proteins and regulators of SNARE complex assembly.
Rabs are activated by specific guanine nucleotide exchange factors (GEFs) that catalyze the displacement of
GDP and binding of GTP and are inactivated by GTPase activating proteins (GAPs) that stimulate the slow
intrinsic rate of GTP hydrolysis. We have proposed that adjacent Rabs on a traffic pathway are networked to
one another through their regulators. The postulated effect of these counter-current cascades is a programmed
series of abrupt Rab conversions that lead to changes in the functional identity of the membrane as it flows
along a pathway. Rabs are also thought to define the anterograde versus retrograde directionality of vesicular
transport. In addition, Rab GEF-effector interactions are believed to generate positive feedback loops that
promote vesicle maturation. While the roles of individual elements of the regulatory network have been
examined, these proposals have not yet been tested at a more global, integrated level. We propose three
specific aims that will address important aspects of the Rab regulatory network:
1. We will test the effects of rewiring a Rab regulatory circuit to evaluate its role in establishing organelle
identity and pursue a novel inhibitory role for a coiled-coil vesicle tether that has emerged from these studies
2. We will directly test the role of Rabs in the control of the directionality of membrane traffic
3. We will determine the role of a Rab GEF-effector interaction in secretory vesicle maturation

## Key facts

- **NIH application ID:** 9968312
- **Project number:** 5R01GM082861-13
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** PETER Jay NOVICK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,500
- **Award type:** 5
- **Project period:** 2008-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968312

## Citation

> US National Institutes of Health, RePORTER application 9968312, Coordination of membrane traffic through rab GEF and GAP cascades (5R01GM082861-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9968312. Licensed CC0.

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