Calcyphosine is a microtubule-associated protein required for spindle formation and function

Abstract

Calcyphosine (CAPS) is a highly conserved but little explored calcium-binding protein that shows elevated expression in many forms of human cancer. Here we uncover a role for CAPS in spindle formation during mitosis. Our experiments suggest that CAPS is a microtubule-binding, spindle-associated protein that helps create the kinetochore fibers that bind and segregate chromosomes. Knockdown of CAPS causes a variety of defects during mitosis, including uncongressed chromosomes and multi-polar spindles, as well as high levels of apoptosis and a reduced mitotic index. We find that CAPS promotes microtubule bundling, both in vitro and in cells, and knockdown of CAPS leads to reduction of thick k-fibers in the mitotic spindle. The high level of CAPS observed in many forms of cancer suggests that CAPS may promote cell proliferation, but our results indicate that CAPS overexpression has little effect on the cell cycle. This suggests that the high level of CAPS expression may be a consequence of cancer, rather than a driving force for cell proliferation.