The ch-TOG/XMAP215 protein is essential for spindle pole organization in human somatic cells.
The ch-TOG/XMAP215 family of proteins bind directly to microtubules and appear to play an essential role in stabilizing spindle microtubules. These proteins stabilize microtubules mainly by influencing microtubule plus-end dynamics, yet, in vivo, they are all strongly concentrated at spindle poles, where the minus ends of the microtubules are concentrated. In Drosophila embryos, the centrosomal protein D-TACC is required to efficiently recruit ch-TOG/Msps to centrosomes. In humans, ch-TOG and the three known TACC proteins have been implicated in cancer, but their functions are unknown. Here we extensively depleted TACC3 and ch-TOG from HeLa cells using RNA interference. In TACC3-depleted cells, spindles are well organized, but microtubules are partially destabilized and ch-TOG is no longer concentrated on spindle microtubules. In ch-TOG-depleted cells, relatively robust spindles form, but the spindles are highly disorganized. Thus, in human somatic cells, ch-TOG appears to play a major role in organizing spindle poles, and a more minor role in stabilizing spindle microtubules that is, at least in part, mediated via an interaction with TACC3.
Gergely
Fanni
F
Department of Pharmacology, University of Cambridge, Wellcome Trust/Cancer Research UK Institute, Cambridge CB2 1QR, UK.
Draviam
Viji M
VM
Raff
Jordan W
JW
D000818:Animals; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*
C454180:CKAP5 protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C120551:TACC3 protein, human