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Updated: Jun 26, 2025
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High-resolution Time-lapse Imaging and Automated Analysis of Microtubule Dynamics in Living Human Umbilical Vein Endothelial Cells
Published on: August 13, 2016
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Extracellular signals induce dynamic ER remodeling through αTAT1-dependent microtubule acetylation
Hannah R Ortiz1, Paola Cruz Flores2, Julia Podgorski1
1Department of Pharmacology, University of Arizona, Tucson, AZ 85724, USA.
Neoplasia (New York, N.Y.)
|May 17, 2024
Summary
External signals regulate endoplasmic reticulum (ER) shape. The TAK1/αTAT1 pathway drives ER tubulation, promoting cell survival by degrading the proapoptotic protein BOK.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Endoplasmic reticulum (ER) morphology dynamics are crucial for cellular homeostasis.
- Microtubules (MT) remodel the ER network, but extracellular signal control is unclear.
Purpose of the Study:
- Investigate how extracellular signals control ER remodeling.
- Identify the molecular pathway linking external stimuli to ER tubulation and cell survival.
Main Methods:
- Utilized cell-based assays to study ER morphology.
- Investigated the roles of TAK1, αTAT1, BOK, and IP3R in ER remodeling.
- Analyzed protein degradation and cell survival mechanisms.
Main Results:
- TAK1 (Transforming growth factor-beta-activated kinase 1) activates αTAT1 (alpha-tubulin acetyltransferase 1), promoting ER tubulation via enhanced MT sliding.
- This TAK1/αTAT1 pathway downregulates the proapoptotic effector BOK.
- BOK degradation is linked to its dissociation from IP3R during ER sheet-to-tubule conversion, enhancing cell survival.
Conclusions:
- Discovered a novel mechanism of ligand-induced ER remodeling controlled by the TAK1/αTAT1 pathway.
- This pathway links extracellular signals to ER structure, promoting cell survival by degrading BOK.
- The TAK1/αTAT1 pathway represents a potential therapeutic target for ER stress and dysfunction.
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