35.7
Spindle Assembly
Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubu…
During eukaryotic cell division, microtubules assemble around the duplicated chromosomes in a bipolar array, forming the spindle apparatus. Spindle assembly is aided by multiple collaborating mechanisms.
Spindle assembly begins after two centrosomes are positioned at opposite ends of the cell. In animal cells, spindle poles are located at the centrosomes.
The centrosomes mature and nucleate bipolar microtubules, where the minus-end is anchored to the spindle pole, and the plus-end radiates outwards.
Simultaneously, multifunctional enzyme complexes, called M-Cdks, phosphorylate several nuclear envelope components, triggering the nuclear envelope to breakdown and expose the condensed chromosomes to the cytoplasm.
Microtubule nucleation at the centrosomes generates three types of microtubules. Interpolar microtubules come from opposite poles whose plus ends overlap, creating an antiparallel array at the spindle midzone. Kinetochore microtubules have their plus-ends connect with the kinetochores of exposed chromosomes. Astral microtubules have their plus-ends contact and interact with the cell cortex, positioning the spindle pole.
In the absence of centrosomes, mitotic chromosomes aid in acentrosomal spindle assembly. Mitotic chromosomes activate Ran-GTP, a nuclear protein. Activated Ran-GTP induces the release of microtubule-stabilizing proteins from protein complexes in the cytosol. The local activation of these factors promotes localized microtubule nucleation and stabilization.
Several microtubule-dependent motor proteins also contribute to spindle assembly and stabilization.
Dynein links astral microtubule plus-ends with cell-cortex components and pulls the spindle poles toward the cell-cortex. In the spindle midzone, kinesin-5 associates with interpolar microtubule plus-ends, to slide them past each other and generate a force that pushes the poles apart.
Kinesin-14 cross-links the interpolar microtubules at the spindle midzone and generates tension that pulls the poles together. Kinesin-4 and kinesin-10, the chromokinesins, connect microtubules with chromosomal arms to push chromosomes away from the poles.
The balance of these opposing forces generated by the motor proteins determines the final length and position of the assembled spindle.
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Q1: What is the spindle and what role does it play in cell division?
The spindle is a dynamic structure composed of microtubules that forms during cell division to organize and separate chromosomes. It extends from opposite poles of the cell and attaches to chromosomes at specialized regions called kinetochores. The spindle ensures each daughter cell receives an identical set of chromosomes during mitosis and cytokinesis.
Q2: How do microtubules organize to form the spindle apparatus?
Microtubules nucleate from centrosomes located at opposite poles of the cell and extend toward the cell's center. These microtubules interact with kinetochore proteins on chromosomes and with other microtubules from the opposite pole. This organized network of microtubules creates the bipolar spindle structure essential for chromosome segregation.
Q3: What are kinetochores and how do they connect to the spindle?
Kinetochores are protein complexes located at the centromere region of chromosomes that serve as attachment points where spindle microtubules bind. This connection allows the spindle to pull sister chromatids apart toward opposite poles during cell division. Proper kinetochore-microtubule attachment is critical for accurate chromosome segregation.
Q4: What happens to the spindle during different phases of mitosis?
During prophase, the spindle begins forming as microtubules extend from centrosomes. In metaphase, spindle fibers align chromosomes at the cell's equator. During anaphase, spindle fibers shorten, pulling sister chromatids to opposite poles. The spindle then disassembles during telophase as the cell prepares for cytokinesis.
Q5: How do centrosomes contribute to spindle assembly?
Centrosomes act as microtubule-organizing centers that nucleate and organize microtubules into the spindle structure. During spindle assembly, centrosomes move to opposite poles of the cell and serve as anchoring points for microtubule arrays. This polar positioning ensures the spindle forms a bipolar structure necessary for proper chromosome segregation.
Q6: What forces move chromosomes along spindle fibers during cell division?
Motor proteins, including kinesins and dyneins, generate forces that move chromosomes along spindle microtubules by using ATP energy. These proteins walk along microtubules, pulling chromosomes toward the poles. Additionally, changes in microtubule length and depolymerization contribute to chromosome movement during anaphase.
Q7: What happens if spindle assembly fails during cell division?
Failed spindle assembly can result in chromosomes not aligning properly or segregating incorrectly to daughter cells. This leads to aneuploidy, where daughter cells receive an abnormal number of chromosomes. Such errors can trigger cell cycle checkpoints that halt division or trigger cell death, preventing propagation of genetically unstable cells.