Paxillin inhibits HDAC6 to regulate microtubule acetylation, Golgi structure, and polarized migration

Polarized cell migration is essential for normal organism development and is also a critical component of cancer cell invasion and disease progression. Directional cell motility requires the coordination of dynamic cell-extracellular matrix interactions as well as repositioning of the Golgi apparatu...

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Bibliographic Details
Published in:The Journal of cell biology 2014-08, Vol.206 (3), p.395-413
Main Authors: Deakin, Nicholas O, Turner, Christopher E
Format: Article
Language:English
Subjects:
Acetylation
Animals
Cell adhesion & migration
Cell Line, Tumor
Cell Movement
Cell Polarity
Cytoskeleton
Extracellular Matrix - metabolism
Golgi Apparatus - metabolism
Golgi Apparatus - ultrastructure
Histone Deacetylase 6
Histone Deacetylases - metabolism
Humans
Mice
Microtubules - metabolism
Motility
NIH 3T3 Cells
Paxillin - physiology
Protein Processing, Post-Translational
Proteins
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Summary:Polarized cell migration is essential for normal organism development and is also a critical component of cancer cell invasion and disease progression. Directional cell motility requires the coordination of dynamic cell-extracellular matrix interactions as well as repositioning of the Golgi apparatus, both of which can be controlled by the microtubule (MT) cytoskeleton. In this paper, we have identified a new and conserved role for the focal adhesion scaffold protein paxillin in regulating the posttranslational modification of the MT cytoskeleton through an inhibitory interaction with the α-tubulin deacetylase HDAC6. We also determined that through HDAC6-dependent regulation of the MT cytoskeleton, paxillin regulates both Golgi organelle integrity and polarized cell invasion and migration in both three-dimensional and two-dimensional matrix microenvironments. Importantly, these data reveal a fundamental role for paxillin in coordinating MT acetylation-dependent cell polarization and migration in both normal and transformed cells.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201403039