FAIDULLA, LANA (2021) Investigating the Interplay Between Cytolinkers and Nesprin-3. Masters thesis, Durham University.
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Author-imposed embargo until 02 August 2024.
The mammalian cytoskeleton is a complex and dynamic network of proteins which function to organise contents of cells, allow cells to respond to external environments, change shape and become motile. Cytoskeletal proteins interact and work with many other proteins in the cytoplasm and nucleus including microtubule actin cross-linking factor 1 (MACF1), plectin and nesprin-3 to achieve these roles. MACF1 is a spectraplakin protein, able to bind all three elements of the cytoskeleton: actin, microtubules and intermediate filaments, linking different cytoskeletal networks together. Through alternative splicing, plectin is expressed as 11 different isoforms and is primarily an intermediate filament binding protein, anchoring intermediate filaments to desmosomes and hemidesmosomes. Nesprin-3 is a member of the LINC complex (Linker of Nucleoskeleton and Cytoskeleton) family of proteins and binds with plectin’s actin-binding domain, establishing a link between the outer nuclear membranes with intermediate filaments.
The relationship between nesprin-3, MACF1a3 (the third isoform of MACF1, produced by alternative splicing) and plectin was investigated using western blotting, immunofluorescence and transfection techniques. Results of these experiments demonstrated that MACF1a3 and nesprin-3 were expressed in varying levels within COS-7, HaCaT, C6 and HDF cells. Overexpression of wild-type nesprin-3a did not promote MACF1a3 recruitment to the nuclear envelope but did result in plectin recruitment to the nuclear envelope. Nesprin- 3 mutation constructs H222Y and A927E also recruited plectin to the nuclear envelope.
|Item Type:||Thesis (Masters)|
|Award:||Master of Science|
|Faculty and Department:||Faculty of Science > Biological and Biomedical Sciences, School of|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||03 Aug 2021 08:57|