The investigation of plasma membrane localization and molecular function of PCDH7 and CLIC4 during cell division

The regulation of the plasma membrane during cell division is essential for maintaining membrane dynamics and cortical stability, both of which are critical for the fidelity of cell division. This thesis investigates the underlying mechanism of two mitosis specific plasma membrane-enriched proteins, PCDH7 and CLIC4, and uncovers their importance in coordinating membrane-cytoskeleton interactions. PCDH7 is identified as a regulator of the actomyosin network during cytokinesis, where it facilitates proper cleavage furrow ingression and completion of cytokinesis. Palmitoylation emerges as an essential mechanism in the translocation of PCDH7 to the plasma membrane at the onset of mitosis through its interaction with a palmitoyl acyltransferase, ZDHHC5. Dynamic plasma membrane localization of PCDH7 promotes the activation of essential cytokinetic regulators, such as RhoA and myosin II, which facilitate actomyosin ring constriction and ensure successful cell division. In contrast, CLIC4 plays a dual role in stabilizing membrane dynamics and cortical tension during cytokinesis. My results suggest that CLIC4 may localize to the plasma membrane in a palmitoylation-dependent manner and bind phosphoinositols, such as PI(3,5)P2 and PI(4,5)P2, to regulate membrane-cytoskeleton interactions. Live-cell imaging reveals its sequential recruitment during the bleb life cycle, where it supports membrane stabilization in the expansion phase and maintains cortical integrity. These findings highlight CLIC4's distinct role in coordinating membrane tension and bleb regulation, processes critical for cell shape maintenance during mitotic progression. Together, the work on PCDH7 and CLIC4 advances our understanding of how protein-membrane interactions contribute to cytokinesis and provides a framework for exploring their broader relevance to cellular architecture and function.