Paxillin spurs cell migration and polarization by suppressing an enzyme that destabilizes microtubules, Deakin and Turner show.
Before a cell can crawl in a particular direction, it has to polarize. One cellular change that makes polarization and migration possible is stabilization of the microtubule cytoskeleton. In addition, the microtubule cytoskeleton helps the Golgi apparatus move in front of the nucleus. Deakin and Turner discovered that both alterations depend on paxillin, a protein that normally controls the structure and dynamics of the focal adhesions where a cell attaches to its substrate.
The researchers found that paxillin blocks the enzyme HDAC6, which disrupts microtubules by removing the acetyl groups that stabilize them. Depleting HDAC6 increased microtubule acetylation, whereas knocking down paxillin in a variety of cell types reduced acetylation. Loss of paxillin also prevented relocation of the Golgi. Deakin and Turner determined that paxillin controls cell migration and invasion through its effects on HDAC6.
Paxillin is a scaffold protein—it provides a platform where other proteins can interact and communicate. The researchers discovered that paxillin and HDAC6 stick together, although it is unclear whether paxillin directly inhibits HDAC6 or relies on other proteins. Paxillin normally operates at cell adhesions, but the researchers also found complexes containing paxillin and HDAC6 scattered around the cell. The authors suggest these far-flung complexes control Golgi reorganization and microtubule stability throughout the cell.
Text by Mitch Leslie