The Role of deltaCaMKII in Skeletal Muscle Development
by Gamya Suryapalli
Developed under the guidance of:
Dr. Thomas Abraham
Pharmaceutical Sciences
Calcium – calmodulin dependant protein kinases are a family of multifunctional protein kinases implicated in various processes such as skeletal muscle plasticity, muscle contraction, long term potentiation, transcription and translation activities to name a few. Skeletal muscle differentiation involves commitment of myoblasts to myogenic process following which cell cycle withdrawal, phenotypic differentiation and cell fusion occur thereby resulting in multinucleated myotube development. Critical role played by calcium dependant signaling pathways in differentiation of cardiac and skeletal muscle has been established. CaMKII inhibitor studies show its involvement in vasopressin-dependant myogenic differentiation of L6 rat skeletal muscle cells. The expression CaMKIIδ in skeletal muscle regeneration and its implication in dystrophic muscle disease has been reported. These studies influenced the current research - investigating the role of CaMKIIδ in differentiating C2C12 skeletal muscle cells. Experiments conducted in the lab show a change in expression of CaMKIIδ isoforms during differentiation in C2C12 cells. Could CaMKIIδ be necessary for the process of differentiation? We hypothesized that CaMKIIδ is essential during induction of myogenesis in C2C12 cells. The hypothesis will be tested by analyzing the number and size of myotubes formed during differentiation in presence of CaMKII inhibitors or by knocking down CaMKIIδ using siRNA. DNA sequencing will be used to identify the CaMKIIδ isoforms that show change in expression during differentiation. A decrease in the number and/or size of myotubes is expected due to treatments. Together, results from the expression and inhibitor or knockdown studies would test the hypothesis and help in determining the fundamental role of CaMKIIδ in skeletal muscle differentiation.
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