Understanding KCC3 and its role in severe peripheral neuropathy
The Delpire lab focuses on understanding basic bioregulatory mechanisms of potassium chloride co-transporters (KCCs) in neurons. In particular, my project focuses on KCC3, which is responsible for cell swelling and maintaining the neuronal intracellular chloride concentration, subsequently affecting gabanergic and glycinergic neurotransmission.
However, mutations arising in the conserved C-terminus of KCC3 can cause severe peripheral neuropathy and varying degrees of agenesis of the corpus callous (ACCPN). Recently, a KCC3 mutation in which a threonine is changed to an alanine in a key regulatory position outside of the C-terminus has been shown to cause peripheral neuropathy but not ACCPN. The goal of my project seeks to identify how key bioregulatory mechanisms can precisely regulate or disrupt KCC3 function. Moreover, my project will pursue new drug targets for KCC3 through Rosetta protein modeling.