Kinetochores grip microtubules with directionally asymmetric strength

Abstract

SUMMARYFor accurate mitosis, all chromosomes must achieve ‘bi-orientation’, with replicated sister chromatids coupled via kinetochores to the plus ends of opposing microtubules. However, kinetochores first bind the sides of microtubules and subsequently find plus ends by directed transport or when side-attached microtubules shorten and bring their ends to the kinetochores. Mitotic accuracy depends on the selective release of erroneous attachments and proposed mechanisms have focused mainly on plus-end attachments. Whether erroneous side-attachments are distinguished from correct side-attachments is unknown. Here we show that side-attached kinetochores are very sensitive to microtubule polarity, gripping six-fold more strongly when pulled toward plus versus minus ends. This directionally asymmetric grip correlates with changes in the axial arrangement of subcomplexes within the kinetochores, suggesting that internal architecture dictates attachment strength. We propose that the kinetochore’s directional grip promotes accuracy specifically during early mitosis, by stabilizing correct attachments even before both sisters have found plus ends.