Onderzoekers van het UMC Utrecht geven in Science online deze week antwoord op een reeds lang openstaande vraag. Hoe verdelen cellen tijdens de celdeling hun verdubbelde chromosomen op de juiste manier? Het eiwit Aurora B blijkt hierbij een cruciale rol te spelen. Een verkeerde verdeling van de chromosomen kan leiden tot kanker, maar ook tot het syndroom van Down.
Abstract:
Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi–orientation). Aurora B kinase regulates chromosome–spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bioriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using fluorescence resonance energy transfer (FRET)—based biosensors to measure localized phosphorylation dynamics in living cells, we found that phosphorylation of an Aurora B substrate at the kinetochore depended on its distance from the kinase at the inner centromere. Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bioriented attachments and activated the spindle checkpoint. Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules.
Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi–orientation). Aurora B kinase regulates chromosome–spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bioriented attachments, but how physical forces are translated into signaling at individual centromeres is unknown. Using fluorescence resonance energy transfer (FRET)—based biosensors to measure localized phosphorylation dynamics in living cells, we found that phosphorylation of an Aurora B substrate at the kinetochore depended on its distance from the kinase at the inner centromere. Furthermore, repositioning Aurora B closer to the kinetochore prevented stabilization of bioriented attachments and activated the spindle checkpoint. Thus, centromere tension can be sensed by increased spatial separation of Aurora B from kinetochore substrates, which reduces phosphorylation and stabilizes kinetochore microtubules.
