Gamma-tubulin regulates the anaphase-promoting complex/cyclosome during interphase
Tania Nayak1, Heather Edgerton-Morgan, Tetsuya Horio
1Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA.
The Journal of Cell Biology
|August 4, 2010
Summary
A mutation in gamma-tubulin disrupts cell cycle regulation by preventing key proteins from accumulating in some nuclei. This leads to noncycling nuclei and inhibited growth, revealing gamma-tubulin
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Gamma-tubulin is essential for microtubule nucleation.
- Cell cycle regulation involves precise protein accumulation and degradation.
- The anaphase-promoting complex/cyclosome (APC/C) controls cell cycle progression.
Purpose of the Study:
- To investigate the function of a cold-sensitive gamma-tubulin allele (mipAD159) in Aspergillus nidulans.
- To determine the effects of mipAD159 on mitotic and cell cycle regulation.
- To elucidate the mechanism by which gamma-tubulin influences cell cycle control.
Main Methods:
- Time-lapse microscopy of fluorescently tagged proteins.
- Analysis of mitotic and cell cycle regulatory proteins (cyclin B, CDK1, Ancdc14).
- Assessment of nuclear cell cycle progression in a multinucleate system.
Main Results:
- The mipAD159 allele caused defects in mitotic and cell cycle regulation at restrictive temperatures.
- Key cell cycle proteins failed to accumulate in a subset of nuclei.
- These nuclei were permanently removed from the cell cycle in a microtubule-independent manner.
- A failure in APC/C inactivation was identified as the cause of noncycling nuclei.
Conclusions:
- Gamma-tubulin plays a critical role in regulating the anaphase-promoting complex/cyclosome.
- Gamma-tubulin's function in cell cycle regulation is independent of its role in microtubule nucleation.
- Dysregulation of gamma-tubulin can lead to cell cycle arrest and growth inhibition.
Related Concept Videos
Microtubule Instability
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
Microtubule Instability
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated assembly and...
Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Anaphase Promoting Complex
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Anaphase A and B
Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
Separation of Sister Chromatids
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...


