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Functional Modulation Of The Cav3.1 Calcium Channel By Alternative Splicing At The C-Terminus, Ruizhi Wang

Theses and Dissertations

The CACNA1G gene encodes for Cav3.1, the alpha-1G subunit of a low-voltage-activated T-type calcium channel, which plays crucial roles in cardiac and smooth muscle cells and neurons by influencing the transmembrane potentials and regulating intracellular Ca2+ signaling. Heterozygous missense mutations in the CACNA1G gene cause spinocerebellar ataxia-42 (SCA42), a heterogeneous group of neurodegenerative disorders characterized by brainstem and cerebellum degeneration, and mice that are null for this gene present severe motor coordination defects, abnormal electrical conductance in the heart, aberrant action potentials in the brain, disrupted sleeping patterns, and absence epilepsy. Different splice variants of Cav3.1 have been described, and …

Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain

Theses and Dissertations

Gene expression is regulated at multiple levels, including transcription, RNA editing, pre-mRNA splicing, mRNA export, translation, and posttranslational modifications. Alternative splicing is a process by which exons can be included or excluded, giving rise to multiple mRNA isoforms from the same transcript. Alternative splicing is an important mechanism in developmental, tissue- and cell-specific control of gene expression, and it is key for expanding proteomic diversity and complexity from a limited number of genes. Moreover, more than 95% of multiexon genes undergo alternative splicing in humans, and about half of all disease-causing point mutations in humans affect pre-mRNA splicing, including neurological …

Investigating The Patterns And Mechanisms Of Alternative Splicing Of Cav1.3 In The Mouse., Samuel Sabzanov

Theses and Dissertations

AL-type voltage-gated calcium channel Cav1.3 contains a pore-forming α-1 subunit that is encoded by Cacna1d, a gene which has been shown to undergo alternative splicing (AS). Mutations in CACNA1D have been associated with neurological diseases such as spontaneous seizure disorder and epilepsy. Previous studies have shown that AS of the C-terminus of Cav1.3 results in a truncated variant of exon 42 (E42) that, when compared to the full-length exon, lowers the voltage threshold needed to activate the calcium channel. Therefore, AS of the a1-subunit can modulate the physiological properties of Cav1.3. As a lower voltage threshold of calcium channels increases …