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Regulation Of Human 69-Kda Choline Acetyltransferase Protein Stability And Function By Molecular Chaperones And The Ubiquitin-Proteasome System, Trevor M. Morey
Regulation Of Human 69-Kda Choline Acetyltransferase Protein Stability And Function By Molecular Chaperones And The Ubiquitin-Proteasome System, Trevor M. Morey
Electronic Thesis and Dissertation Repository
The enzyme choline acetyltransferase (ChAT) mediates synthesis of the neurotransmitter acetylcholine required for cholinergic neurotransmission. ChAT mutations are linked to congenital myasthenic syndrome (CMS), a rare neuromuscular disorder. One CMS-related mutation, V18M, reduces ChAT enzyme activity and cellular protein levels, and is located within a highly-conserved N-terminal proline-rich motif at residues 14PKLPVPP20. It is currently unknown if this motif regulates ChAT function. In this thesis, I demonstrate that disruption of this proline-rich motif in mouse cholinergic SN56 cells reduces both the protein levels and cellular enzymatic activity of mutated P17A/P19A- and V18M-ChAT. The cellular loss …