Cell division is a complex process. At the heart of this complexity is a membrane-less organelle called the centrosome, which is made up of more than 200 components. It is responsible for the clustering of mitotic spindles, thread-like structures needed for separation of genetic material. Which parts of the centrosome are necessary and sufficient for this spindle assembly has long remained elusive.
Researchers at the Department of Microbiology and Cell Biology (MCB), Indian Institute of Science (IISc), have now developed a new technique called Light-Induced Spindle Activation (LISA), which can reversibly activate Aurora A kinase, a key centrosomal enzyme critical for spindle assembly. Their technique allows scientists to study centrosomes and spindle assembly in much greater detail. It also opens the door to the possibility of rescuing cell division by artificially manipulating these components and processes when they fail. The study was published in EMBO Reports .
Scientists believed that Aurora A is activated through clustering, a process promoted in cells by its evolutionarily conserved scaffold, Cep192. Previous work has shown that Aurora A-coated beads can trigger microtubule nucleation in frog egg extracts; however, Cep192 is required for Aurora A activation in this setting. With LISA, researchers can now reversibly induce and study Aurora A clustering using blue light, independently of Cep192, across a range of cell types. LISA can also be applied directly in living cells, whereas the bead-based method is largely restricted to cell extracts.
To develop this method, Sachin Kotak, Associate Professor at MCB, and his team identified a novel application for an existing technique called LARIAT, which is typically used to inhibit proteins by inducing their clustering with light. Kotak’s team realised that this light-induced clustering could instead be harnessed to activate Aurora A kinase. LARIAT uses the plant proteins CRY2 and CIB1, which can be induced to cluster in response to blue light.
The researchers first engineered human cells to express a fusion protein in which Aurora A kinase was linked to CRY2. When blue light is shined on the fusion protein, CRY2 undergoes a conformational change that promotes its interaction with CIB1. This, in turn, drives the clustering of multiple Aurora A assemblies, explains Vignesh Olakkal, PhD student in Kotak’s lab and first author of the study. “This provides a novel way to trigger and activate an artificial Aurora A kinase complex – Aurora A fused to light-sensitive plant proteins, which is sufficient to induce microtubule nucleation,” he adds.
Cells without centrosomes often have defects in spindle assembly, leading to errors in cell division. Kotak’s team wanted to test whether LISA could overcome this defect. They first chemically eliminated the centrosomes from human cells and then introduced the engineered Aurora A clustering system. When blue light was applied during mitosis, it induced Aurora A clustering and efficiently stimulated microtubule nucleation. Remarkably, this light-induced activation of Aurora A was sufficient to restore spindle assembly and rescue defects in cell division caused by centrosome loss.
LISA also has potential therapeutic applications, according to the researchers. “In many solid tumours, Aurora A kinase is overexpressed, and that’s why there are drugs targeting it. But Aurora A kinase has multiple targets,” Kotak explains. “Now, with our strategy, we can find out what the Aurora A kinase-specific targets are, independent of the centrosome, as far as microtubule nucleation is concerned. Then we will hopefully be able to find other targets of Aurora A kinase and design drugs.”
EMBO Reports
Light-induced spindle assembly through Aurora A clustering
15-Sep-2026