DOI

10.17077/etd.rfrwubsw

Document Type

Dissertation

Date of Degree

Spring 2018

Degree Name

PhD (Doctor of Philosophy)

Degree In

Molecular Physiology and Biophysics

First Advisor

Christopher A. Ahern

First Committee Member

Sheila Baker

Second Committee Member

Charles Harata

Third Committee Member

Robert Piper

Fourth Committee Member

Janice Robertson

Fifth Committee Member

Julien Sebag

Abstract

Voltage-gated sodium channels auxiliary subunits evolutionary emerged nearly 500 million years ago during the Cambrian explosion. These subunits alter one the most important ion channels to electrical signaling, the voltage-gated sodium channels support the propagation of electric impulses in animals. The mechanism for the auxiliary subunits effects on the channels is poorly understand, as is the stoichiometry between the auxiliary subunit and the channel. The focus of my thesis is to generate assays and to use these approaches to understand the interactions different types of voltage-gated channels and their auxiliary subunits. A biochemical approach was taken to identify novel interactions between the eukaryotic sodium channel auxiliary subunits and a prokaryotic voltage-gated sodium channel, a protein that diverged from the eukaryotic voltage-gated sodium channels billions of years ago. These interactions between the auxiliary subunits and channels were probed with chemical and photochemical crosslinkers in search of interaction surfaces and similarity to explain the mechanisms of interaction. The work in this thesis identified novel interactions between the voltage-gated sodium channel auxiliary subunits and voltage-gated channels that are distantly related to the voltage-gated sodium channels principally thought to be modulated by the auxiliary subunits. From this work a rudimentary concept can be theorized that the voltage-gated sodium channel β-subunits and not only β1 have a more primary role in electrophysiology by associating with multiple different types of ion channels.

Keywords

Co-affinity purification, Ion channels, Protein-protein interaction, Voltage-gated sodium channel auxiliary subunits

Pages

xv, 146 pages

Bibliography

Includes bibliographical references (pages 135-146).

Copyright

Copyright © 2018 Steven Molinarolo

Included in

Biophysics Commons

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