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Scientists uncover the molecular mechanisms behind spindle elongation in human cells

A recent study on human cell division has revealed the two motor proteins that are responsible for spindle elongation during anaphase B.

Cell division is when a parent cell divides into two or more daughter cells. The process is crucial for the stable transmission of genetic information. Anaphase is the fourth phase of cell division and it consists of two parts – anaphase A and anaphase B. During anaphase A, sister chromatids segregate into future daughter cells. Anaphase B involves the process of spindle elongation.

The spindle elongation process

Mitotic spindles are dynamic and complex cellular structures that are made up of microtubules and associated proteins. The microtubules provide tracks for the transport of chromosomes into the correct position during cell division. Later, the spindles elongate to aid the physical separation of the chromosomes into sister chromatids, and therefore two future daughter cells.

Spindle elongation happens during anaphase in all eukaryotes, including humans. The process is highly important because it is the main driver of chromosome movement. It also promotes the correct segregation of any lagging chromosomes. Defects of spindle processes have been associated with cancer.

Although some candidate proteins have been implicated in spindle elongation, until recently the molecular mechanism that drives the process in human cells had not been revealed.

Spindle research

Recently, researchers at the Croatian Ruđer Bošković Institute (RBI) uncovered the precise molecular mechanism behind the sliding of spindle microtubules and the role that it plays in the distribution of genetic material during cell division.

The studies combined assays and CRISPR technology to systematically explore the interactions between the motor proteins during anaphase B. Effectively, the goal was to understand which motor proteins were responsible for spindle elongation.

The results were as follows:

  • Anaphase spindle elongation was independent of individual activities of EG5/kinesin-5 and PRC1-dependent motors.
  • The elongation was driven by redundant EG5 and PRC1 protein modules.
  • The plus-end-directed motor proteins KIF4A and EG5 were crucial for spindle elongation.
  • The kinesin-6MKLP1 and kinesin-6 MKLP2 played supporting roles in the process.
  • Increase in the stability of midzone microtubules was not essential for spindle elongation during early anaphase.
  • Astral microtubules were not crucial for spindle elongation.
  • KIF4A and EG5 slid midzone microtubules apart.

Essentially, it was found that the force-generating mechanism of spindle elongation consists of two motor proteins that work together – KIF4A and EG5. Interestingly, it was also discovered that the motor protein KIF4A was dependent on a non-motor microtubule associated protein, called PRC1.

The future of spindles

The research uncovered, for the first time, that two mechanistically distinct modules are responsible for powering the mechanism of spindle elongation. The results suggest that anaphase B is a process driven by independent protein systems that are each likely to have unique mechanisms of both action and control. These independent modules are probably what enables the very high success rate of anaphase.

The research also showed that the consequences of unsuccessful elongation during anaphase were devastating for the balance of inherited genetic material. Therefore, future studies into spindle mechanisms are critical for improving our understanding of genetic diseases caused by failures in cell division.

Professor Iva Tolić, a leader of the research, explained:

“We hope these results will encourage new research into the role of spindle elongation. I believe these results are just the first step on a path of elucidating the complex control mechanisms acting behind these motor proteins, which operate under strict control of many other factors in the cell. Moreover, the principle of co-operation between these motor proteins, that we have described, could help other scientists in determining molecular mechanisms in other crucial cell processes.”

Image credit: GiovanniCancemi

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