Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator.
A putative spindle matrix has been hypothesized to mediate chromosome motion, but its existence and functionality remain controversial. In this report, we show that Megator (Mtor), the Drosophila melanogaster counterpart of the human nuclear pore complex protein translocated promoter region (Tpr), and the spindle assembly checkpoint (SAC) protein Mad2 form a conserved complex that localizes to a nuclear derived spindle matrix in living cells. Fluorescence recovery after photobleaching experiments supports that Mtor is retained around spindle microtubules, where it shows distinct dynamic properties. Mtor/Tpr promotes the recruitment of Mad2 and Mps1 but not Mad1 to unattached kinetochores (KTs), mediating normal mitotic duration and SAC response. At anaphase, Mtor plays a role in spindle elongation, thereby affecting normal chromosome movement. We propose that Mtor/Tpr functions as a spatial regulator of the SAC, which ensures the efficient recruitment of Mad2 to unattached KTs at the onset of mitosis and proper spindle maturation, whereas enrichment of Mad2 in a spindle matrix helps confine the action of a diffusible "wait anaphase" signal to the vicinity of the spindle.
Lince-Faria
Mariana
M
Instituto de Biologia Molecular e Celular, Faculdade de Medicina, Universidade do Porto, 4150-180 Porto, Portugal.
Maffini
Stefano
S
Orr
Bernard
B
Ding
Yun
Y
Cláudia Florindo
Sunkel
Claudio E
CE
Tavares
Alvaro
A
Johansen
Jørgen
J
Johansen
Kristen M
KM
Maiato
Helder
H
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002875:Chromosomes / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D036681:Fluorescence Recovery After Photobleaching; D018816:Genes, cdc / Q000502:physiology; D018386:Kinetochores / Q000378:metabolism / Q000648:ultrastructure; D064246:Mad2 Proteins; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008938:Mitosis / Q000502:physiology*; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D064246:Mad2 Proteins; C498867:Mtor protein, Drosophila; D034521:Nuclear Matrix-Associated Proteins; D011494:Protein Kinases; C501876:Mps1 protein, Drosophila; D017346:Protein Serine-Threonine Kinases