The nuclear envelope protein – Sun1 : its role in mechanosignaling and cytoskeletal dynamics.

• Main Author: Phua, Siew Cheng.
• Other Authors: School of Biological Sciences
• Format: Final Year Project
• Language: English
• Published: 2010
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: http://hdl.handle.net/10356/38875
• Institution: Nanyang Technological University

The LINC (LInker of Nucleoskeleton and Cytoskeleton) complex establishes evolutionarily conserved connections between the nuclear lamina and cytoskeleton. Disruption to the LINC complex has been proposed to contribute to the molecular pathophysiology of laminopathies, a group of genetic diseases caused by mutations of the nuclear lamin A (LMNA) gene. The objective of this project is to determine how loss of a specific component of the LINC complex, Sun1, affects the interactions between the cytoskeleton and nucleus and whether this has effects on gene expression. Results suggest that, depending on the cell type, the effects of loss of Sun1 may be variable. Absence of Sun1 in myotubes results in reduced expression of lamin A/C, suggesting that interactions between them may promote the accumulation of nuclear lamins in NE. The polarization of Sun2 distribution in Sun1 KO myonuclei also suggests a possible compensatory mechanism acquired by cells lacking Sun1. Such effects were not observed in Sun1 KO fibroblasts. Furthermore, preliminary mechanotransduction studies also suggest defective mechanosignaling responses in Sun1 KO cells. Overall, results support the involvement of Sun1 in regulating cytoskeletal dynamics and gene expression. Further research would provide useful insights in the involvement of LINC complexes in the molecular pathophysiology of laminopathies.