The microtubule cytoskeleton also participates in the maintenance of epithelial planar polarity by modulating the orientation of the mitotic spindle. The organization of epithelial cells to form hollow organs with a single lumen implies that each cell divides symmetrically within the epithelial plane, so that both resulting daughter cells remain in the same plane. Thus, mitotic spindles must orient within the planar axis. Perpendicular divisions, however, are necessary to create stratified epithelia. Defective spindle orientation damages the axis of cell division and could eventually disrupt epithelial organization and generate unrestrained daughter cells from contact with neighbors. Mitotic spindle positioning in most epithelia is controlled by astral microtubules that are nucleated at the spindle poles and orient their plus ends toward the cell cortex. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay There are two main events that determine spindle orientation: creation of a polarity axis by the distorted distribution of polarity proteins in the cell cortex; ealignment of the mitotic spindle with respect to this polarity axis by “capturing” microtubule ends at these cortical points. Cortical proteins that determine spindle alignment generate distorted spindle orientation by establishing physical connections with astral microtubule end-binding proteins and stabilize these otherwise highly dynamic structures. Cortical protein complexes that interact with the plus ends of astral microtubules include the Gai/LGN complex, which is recruited to the lateral membrane by Dlg and E-cadherin and excluded from the apical membrane by phosphorylation of aPKC. In turn, the LGN interacts with the “nuclear mitotic apparatus” (NuMA), which binds to dynein/dynactin, the motor protein responsible for the pulling force of the astral microtubules that directs spindle movement. Another cortical protein complex composed of cdc42 and junctional adhesion molecule A (JAM-A) that promotes dynein/dynactin accumulation on the lateral membrane was also identified. Much less is known about the molecular players that regulate spindle orientation in the spindle apparatus. Please note: this is just an example. Get a custom paper from our expert writers now. Get a Custom Assay End-binding protein 1 (EB1) is an autonomous plus end-binding protein that regulates the dynamic instability of microtubules by increasing periods of microtubule growth and decreasing periods of microtubule breakage. In addition to its role in the formation and stabilization of spindle microtubules, studies in Drosophila have indicated that EB1 is a crucial factor for spindle orientation during symmetric planar division in epithelial cells. Our studies in three-dimensional epithelial cell cultures showed that EB1 is loaded on astral microtubules at the spindle poles and that its presence in these structures is essential for spindle orientation and accurate lumen formation. Although the exact mechanism governing EB1-directed spindle orientation has not been elucidated, EB1 is a scaffold that recruits specific proteins to microtubule ends, including the glued dynactin subunit p150 and the polarity protein Par1, both involved in spindle orientation. The glued P150 regulates spindle orientation, likely enhancing dynein processivity.