Biology Reference
In-Depth Information
SUMMARY
Microtubule detachment from centrosomes and spindle poles is a poorly understood
process whose importance is only now becoming appreciated. It was initially pro-
posed to play a role in cytoplasmic microtubule turnover (
Keating et al., 1997
),
but more recent studies have demonstrated that it is a cell cycle-regulated process
that plays a critical role in cell division and in the mechanism of action of drugs that
affect mitotic spindle formation (
Ganguly & Cabral, 2011
). These drugs either stim-
ulate (e.g., colchicine, vinblastine, nocodazole) or suppress (e.g., paclitaxel, epothi-
lones) microtubule detachment indicating that the frequency of detachment must be
maintained at appropriate levels for normal mitotic progression. Tubulin mutations
that interfere with cell division often act by stimulating microtubule detachment, and
their effects can be counteracted by depletion of MCAK (
Ganguly, Yang, Pedroza,
et al., 2011
). Similarly, toxic effects due to overexpression of MCAK can be counter-
acted by treatment with paclitaxel (
Ganguly, Yang, Pedroza, et al., 2011
). Hence, it is
likely that kinesin-related proteins such as MCAK play a significant role in the mech-
anism of detachment, and future studies will be needed to determine what other pro-
teins are involved in the mechanism and how those proteins are arranged and
regulated. More work will also be needed to determine how the microtubules are re-
leased and the role that microtubule detachment plays during cell division. Is detach-
ment necessary to remodel the interphase microtubules when cells enter mitosis?
Does it provide microtubule fragments for mitotic spindle assembly? Does it occur
continuously throughout mitosis or only at specific stages? Attempts to answer these
and related questions will provide exciting challenges for years to come.
Acknowledgments
We thank Dr. Joanna Olmsted for the EGFP-MAP4 used in our studies. This work was gen-
erously supported by NIH Grant CA85955 to F. C.
References
