Formation of a polarized epithelial cell requires rearrangement of the cell's microtubules. As the flat cell rises up into a column, the microtubules are formed into a complex network consisting of bundles aligned from the top to the bottom of the cell, and a meshwork of shorter filaments underneath the basal and apical membranes. Bowen et al. (J. Cell Biol. 194, 187–197; 2011) now show that septin GTPases are needed to guide the microtubule network.

Using immunofluorescence microscopy, the authors found that in polarizing MDCK cells septin filaments overlap with perinuclear microtubule bundles and the distal ends of peripheral microtubules. Knockdown of SEPT2 (a member of the septin family) or expression of a dominant-negative SEPT2 mutant disrupted the spatial organization of the microtubules within the cell, compared with controls. To understand this, the authors performed timelapse microscopy, which showed that microtubules moved along septin filaments as they grew. Knockdown of SEPT2 resulted in a loss of microtubule directionality and the microtubules ended up becoming entangled. Furthermore, SEPT2 knockdown increased microtubule shrinkage, suggesting septins inhibit microtubule depolymerization and thus maintain persistent microtubule growth.

Hence, septin control of microtubule growth and directionality seems to allow for correct organization of microtubules in establishing a polarized epithelial cell.