How signaling between cells can orient a mitotic spindle.

In multicellular animals, cell communication sometimes serves to orient the direction in which cells divide. Control of division orientation has been proposed to be critical for partitioning developmental determinants and for maintaining epithelial architecture. Surprisingly, there are few cases where we understand the mechanisms by which external cues, transmitted by intercellular signaling, specify the division orientation of animal cells. One would predict that cytosolic molecules or complexes exist that are capable of interpreting extrinsic cues, translating the positions of these cues into forces on microtubules of the mitotic spindle. In recent years, a key intracellular complex has been identified that is required for pulling forces on mitotic spindles in Drosophila, Caenorhabditis elegans and vertebrate systems. One member of this complex, a protein with tetratricopeptide repeat (TPR) and GoLoco (Gα-binding) domains, has been found localized in positions that coincide with the positions of spindle-orienting extracellular cues. Do TPR-GoLoco proteins function as conserved, spatially regulated mediators of spindle orientation by intercellular signaling? Here, we review the relevant evidence among cases from diverse animal systems where this protein complex has been found to localize to specific cell-cell contacts and to be involved in orienting mitotic spindles.