Graduation Date

Summer 8-14-2026

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Molecular Genetics & Cell Biology

First Advisor

Subu Ramanathan, PhD

Abstract

The most dramatic cell shape change occurs during mitosis, where elongated cells become spherical to initiate cell division, a phenomenon known as ‘mitotic cell rounding’. The cell cortex elements, predominantly Myosin II activity along with F-actin, are the key drivers that influence this process, simultaneously with increased intracellular pressure due to ion fluxes. However, the details of the mechanism by which intracellular pressure is established during mitotic cell rounding remain unclear. The Na+/H+ antiporter-induced ion influx is essential to drive this process; surprisingly, some reports mark the distinct roles of Ca+2 during mitosis. This study will investigate the role of Ca+2 and the store-operated calcium entry pathway (SOCE)-mediator ORAI1 channel role in the maintenance of mitotic cell shape. To determine the capacity for maintaining mitotic cell shape, we employed atomic force microscopy to confine a single mitotic cell during pharmacological calcium perturbations. Upon Ca+2 elevation and reduction, mitotic cells did not show significant force change or alterations in cell shape. Thapsigargin treatment led to an elevation in mitotic cell force while preserving the mitotic shape. On the other hand, ORAI1 channel inhibition impaired mitotic cell shape by the formation of blebs at the actin cortex. siRNA knockdown of ORAI1 also confirmed our chemical inhibition results, with giving a rise to a disrupted mitotic cell shape. Our results indicate that ORAI1 inhibition can impair mitotic cell shape by accelerating the detachment of F-actin from the underlying cortex. The ORAI1 channel is the key driver to govern mitotic cell shape.

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