Spindles go haywire when there is too much (left) or too little (right) LGN.


Much to their surprise, Ian Macara and colleagues (University of Virginia School of Medicine, Charlottesville, VA) have ended up studying not spindle rotation, but spindle construction.

Their protein of interest, LGN, is the human counterpart of the Drosophila protein Partner of inscuteable (Pins), which helps localize the apical determinant Inscuteable (Insc). Du et al. figured that they could study LGN-mediated spindle rotation using mammalian epithelia, as in these cells the prometaphase spindle rotates to reach its final metaphase orientation. But instead they found that LGN is needed for the construction of the spindle.Overexpression of LGN appears to disrupt microtubule attachment to spindle poles, whereas a lowering of LGN levels using RNAi results in the formation of multiple poles. Thus, LGN may inhibit spindle pole formation, perhaps via an interaction with NuMA that Du et al. detect using multiple methods. NuMA is normally transported to spindle poles where it anchors and focuses microtubules. How LGN might affect this process is unknown, but the entry of LGN into the nucleus at the end of prophase (when the nuclear envelope breaks down) may restrict spindles such that they form only two poles. ▪


Du, Q., et al.
Nat. Cell Biol