'Molecular motors' involved in chromosome transport observed

Researchers at Waseda University in Japan have for the first time directly observed the "molecular motor," called Xkid, that plays a critical role in facilitating the proper alignment of chromosomes during cell division. Their findings are expected to contribute greatly to elucidating the molecular mechanisms of chromosome segregation, a key aspect of the development of certain medical disorders including cancer and birth defects.

Within each cell, Xkid molecules are located inside the spindle apparatus, a structure required for cell division that's composed of a bundle of microtubules. Determining the movements of Xkid in natural spindles is considered the key to understanding the mechanisms of chromosomal segregation during cell division.

While a human body is composed of many different parts such as muscles, internal organs, and a brain, its origin is only a single cell, a fertilized egg, which keeps dividing to form the human being. At every step of the cell division, chromosomes must be precisely segregated without any kind of misplacement between two daughter cells. Chromosomes are the source of all genetic information, and incorrect chromosome segregation can cause various forms of medical disorders including severe illnesses and malignant transformation of tumors.

The Xkid molecular motor is known to play a critical role in facilitating the proper alignment of chromosomes during cell division. Previously, its motor functions have been investigated in vitro using purified Xkid molecules obtained from cell extracts, showing their plus end-directed movement as ensembles of molecules along the microtubules. How such molecular motors behave within intact spindles, however, remained to be characterized. In a cell, Xkid molecules are located within the spindle apparatus, a structure required for cell division. The spindle apparatus is an orderly structure composed of a bundle of numerous microtubules. Elucidating Xkid movements in natural spindles is the key to understanding the mechanisms of chromosome segregation during cell division.

Accordingly, the present study set out to examine the movements of Xkid within an intact spindle.

Techniques developed during the study

We found that Xkid traveled long distances (mean ≈5 µm; maximum 17 µm) along the oriented bundle of microtubules, moving from one microtubule to another along the way. We also observed Xkid moving mostly in the direction corresponding to the distribution of microtubule polarity, leading to the accumulation of Xkid near the spindle equator. This is consistent with the assembly and alignment of chromosomes near the spindle equator in metaphase.

Our findings are the first molecular-level demonstration of the role of Xkid in directing chromosomes toward the spindle equator. Near the spindle poles, more Xkid molecules moved in the equator mode (toward the spindle equator), whereas near the spindle equator, all modes of motion were seen equally frequently (A). The distributions of polarity and length of microtubules were symmetrical with respect to the spindle equator, and corresponded with the predominant direction of Xkid movements (B). The size of the circles representing Xkid-Qdot (quantum dot) indicates the proportion of direction of movement in each location within the spindle.