Regulation of membrane trafficking by Coronins

NIH RePORTER · NIH · R01 · $78,627 · view on reporter.nih.gov ↗

Abstract

ABSTRACT The long-term goal of the parent grant (1R01GM138448-01A1) is to get a better understanding of how the extensive family of the Coronins transduces cellular signaling cues into actin network remodeling to support cell migration, intracellular transport and cytokinesis. Coronins are bona fide actin-binding proteins, however they do not directly alter actin filament dynamics. Instead, they function as signaling scaffolds that recruit a host of other actin-remodeling and actin- regulatory proteins that work in concert to alter actin network architecture and/or dynamics. Most of our understanding of the Coronins stems from studies on the structurally and functionally related short Coronins (Coro1-6), but next to nothing is known about the long or tandem Coronins (Pod-1, Coro7). Leveraging the expertise of the lab in single molecule TIRF microscopy, we are investigating how Coro7 regulates actin filament dynamics, directly as well as indirectly through interaction with actin-regulatory proteins, including the other Coronins. Additionally, we have performed an in-depth proteomic analysis to build the first Coro7 interactome and developed several Coro7 CRISPR knockout cell lines. Combined with our insights gained from the biophysical and biochemical characterization of Coro7, we will use these tools to determine how Coro7 mechanistically regulates cell migration and intracellular trafficking, and by extension tumor cell metastasis and invasion.

Key facts

NIH application ID
10980713
Project number
3R01GM138448-04S1
Recipient
WASHINGTON UNIVERSITY
Principal Investigator
Silvia Jansen
Activity code
R01
Funding institute
NIH
Fiscal year
2024
Award amount
$78,627
Award type
3
Project period
2021-05-01 → 2025-04-30