Presentation description

Endoplasmic reticulum and plasma membrane come into close apposition to form specialized membrane domains (ER-PMs). While ER-PMs are present throughout a wide range of eukaryotic cells, the proteomics of specifically, ion channel associated neuronal ER-PMs is a field of ongoing research. We've known about neuronal ER-PMs for a long time but only recently are looking at proteins enriched at these sites and mutations of thereof being linked to disease phenotypes. Voltage-gated potassium ion channels (Kv's) open in response to the depolarization of the plasma membrane allowing for rapid efflux of K+ ions and, in conjunction with voltage-gated sodium ion channels, play a fundamental role in both the preservation and propagation of the action potential as well as the maintenance of plasma membrane potential homeostasis. Kv-enriched ER-PMs can utilize 10% of the available area on neuronal plasma membranes, the biological significance of such a large cellular allocation to these domains, coupled with their exclusivity to excitatory cells, leads us to hypothesize that they play a crucial role in the neuron's summation, interpretation, and response to stimuli. Transmembrane protein 240 (TMEM240) has been observed to co-localize with high affinity to Kv-enriched ER-PMs, a mechanism successfully recapitulated in transfected HEK-293T cells. The coupling of this co-localization to TMEM240's high concentrations throughout a diverse range of brain tissues and it is characterized that mutations of TMEM240 are implicated in the pathogenesis of the neurodegenerative disease, spinocerebellar ataxia. We believe that TMEM240 is integral to the functionality of ion channel associated ER-PMs. We will be studying the impact of TMEM240 and its variants on the regulation of endocytosis of ER-PMs as well as its subcellular location and orientation. The endeavor to better characterize TMEM240 is a component of our greater project to better understand and categorize the proteins present and their functions at ion channel associated ER-PMs.