Removal of dynein from acentrosomal spindles causes poles (magenta) to split apart, disrupting the organization of the microtubules (green) that make up the spindle and the separation of chromosomes (white). Image credit: Gabriel Cavin-Meza (CC BY 4.0)
Meiosis is a specialized form of cell division that produces the gametes required for sexual reproduction, such as egg and sperm cells. Before the cell splits, it copies its genome so that it has four sets of chromosomes. Genetic information is then shuffled between the chromosomes, and the cell undergoes two rounds of division, resulting in four gametes that are genetically distinct.
Prior to division, the duplicated chromosomes are separated by rope-like protein polymers called microtubules. In most cells, structures called centrosomes organize these fibers into a spindle shape that emanates from two ‘poles’ on opposite ends of the cell: the microtubules then attach to the chromosomes and pull them apart. Despite not having centrosomes, egg cells, or ‘oocytes’, are still able to arrange their microtubules into a similar bipolar shape. However, how oocytes form these ‘acentrosomal’ spindles is poorly understood.
Centrosomes do not organize the spindle alone, and receive help from various motor proteins such as dynein. Previous work showed that dynein is involved in arranging acentrosomal poles, but it was not known if it was required to hold the poles together after they initially formed. To investigate, Cavin-Meza et al. developed a strategy that can rapidly remove dynein from oocytes of the roundworm Caenorhabditis elegans.
The experiment showed that dynein is required both to assemble and stabilize acentrosomal spindles in C. elegans. When dynein and an additional motor protein, KLP-18, were both removed from oocytes simultaneously, the poles blew apart, completely disrupting spindle organization. Surprisingly, Cavin-Meza et al. found that the spindles were able to reform and separate the chromosomes. Further probing revealed, for the first time, that a third motor protein (called BMK-1) also helps to organize the spindle into its bipolar structure.
These findings reveal the important role motor proteins play in stabilizing spindles and separating chromosomes in oocytes. Meiosis is prone to mistakes, and these errors are a major cause of miscarriages and birth defects in humans. Therefore, understanding the underlying mechanisms of how oocyte spindles form and remain stable could shed light on why chromosomes sometimes fail to segregate. This may eventually lead to new strategies for combating infertility.
