Related Experiment Video

Updated: Jul 7, 2025

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

10.9K

Controlled Plasma Membrane Delivery of FGFR1 and Modulation of Signaling by a Novel Regulated Anterograde RTK

Claire Leist Hinsch1,2, Jagadish Kummetha Venkata1,2, Tien Hsu3

  • 1Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29401, USA.

Cancers
|December 23, 2023
PubMed

Insights

Fibroblast growth factor receptor 1 (FGFR1) is sequestered in intracellular vesicles. A novel Regulated Anterograde RTK Transport (RART) pathway controls its delivery to the plasma membrane (PM) upon stimulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Fibroblast growth factor receptor 1 (FGFR1) localization to the plasma membrane (PM) is crucial for cell signaling.
  • FGFR1 is typically assumed to be continuously delivered to the PM, but evidence suggests intracellular sequestration.

Purpose of the Study:

  • To investigate the intracellular dynamics and localization mechanisms of human FGFR1.
  • To identify the molecular components and pathways regulating FGFR1 transport to the PM.

Main Methods:

  • Live-cell imaging and total internal reflection fluorescence microscopy (TIRFM) were used to observe FGFR1-positive vesicles.
  • Recombinant proteins were designed to manipulate transport components.
  • Mouse embryoid bodies (mEBs) served as a 3D model system.

Main Results:

  • FGFR1 is primarily sequestered in intracellular post-Golgi vesicles (PGVs) under normal conditions.
  • Rab2a, Rab6a, Rab8a, RalA, and caveolins are identified as components of these novel FGFR1-positive vesicles.
  • Serum starvation and hypoxia trigger FGFR1 PM localization by inactivating Rab2a and activating the Rab6a-Rab8a-RalA-exocyst pathway.

Conclusions:

  • A novel pathway, Regulated Anterograde RTK Transport (RART), controls FGFR1 delivery to the PM.
  • This represents the first identified mechanism regulating receptor tyrosine kinase (RTK) localization through controlled PM delivery.
Keywords:
FGFR1RART pathwayRTK signalingreceptor traffickingsolid tumors

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