Scientists Uncover How a Key Protein Controls Spindle Fiber Assembly

Every time an animal cell divides, its chromosomes must be sorted and pulled apart with precision. Spindle fibers—the molecular machinery that manages this process—grow from each end of the cell, pushing and pulling chromosomes into position. Yet exactly how cells control where and when those spindle fibers form has remained an open question. A new study offers a detailed answer.

Scientists from the Okinawa Institute of Science and Technology and the University of California, San Diego have identified the exact mechanism by which a protein called SPD-5 regulates the assembly of spindle fibers in the roundworm C. elegans. The findings, published in Science Advances, show that SPD-5 is activated through a precise, step-by-step process that changes the protein's shape, unlocking the binding sites needed to initiate spindle fiber formation. 

Spindle fibers grow primarily from structures called centrosomes—the main spindle construction site in dividing cells. Centrosomes consist of two core structures called centrioles, surrounded by a cloud of proteins that expands when a cell prepares to divide. In C. elegans, SPD-5 is the primary component of that cloud, and it plays a critical role by binding to and activating γ tubulin complexes, which serve as starting points for the microtubules that make up spindle fibers.

"If they aren't formed or regulated properly, chromosomes can segregate incorrectly. This can lead to an abnormal number of chromosomes within a cell, cancer, or developmental diseases like microcephaly, which affects brain development," said first author Midori Ohta.

Before activation, SPD-5 holds itself in a built-in "off" state—folded in on itself like a clenched fist—with the two binding sites responsible for grabbing a γ tubulin complex blocking each other. As the cell prepares to divide and SPD-5 is incorporated into the growing protein cloud at the centrosome, another protein adds chemical phosphate tags to SPD-5. This reshapes the protein, loosening its folded structure and freeing one binding site. That interaction then triggers a further shift, releasing the second site and strengthening the connection to the γ tubulin complex. The result is a step-by-step activation that bypasses SPD-5's built-in safety lock.

The team now plans to investigate the CDK5RAP2 family, the human counterpart of SPD-5, to determine whether the same mechanism applies. "By understanding the fundamental mechanisms that control spindle formation with such precision, we hope to gain important insight into how errors in this process can contribute to human disease," Ohta said.