Contacts in the nervous system: Structural insights into contactin mediated neural adhesion & signaling

Abstract

Proteins are nanoscale molecular machines with a panoply of functions regimenting ubiquitous biological processes across life on earth. Functions of proteins range from nutrient transport, rate enhancement of chemical reactions, to making up structures that make up living things. From the most complex multicellular organisms such as animals or plants, to the more simplistic unicellular organisms such as E.coli, all living things on earth share defining cellular features of which perhaps the most striking is the cellular membrane. The cellular or “plasma” membrane, made up of a lipid bilayer separates the interior of a cell from the exterior environment. This interface serves as a hub which cells communicate with their environment and each other. Cellular membranes across different organisms are made up from distinct assortments of molecules. Such assortments of molecules have a long history under evolutionary pressure, which has led to the emergence of intricate molecular mechanisms controlling diverse biological processes. For formation of complex organisms, processes such as cellular recognition and communication are required and tightly controlled by intricate molecular mechanisms involving diverse molecules. In this dissertation, work on structural and biophysical characterization of vertebrate cell surface contactin proteins is presented. An integrative and multidisciplinary approach is pursued, using structural insights gained from experiments to inform on biological function of contactins in wiring the nervous system in vertebrates. Provided structures inform current knowledge in the molecular basis of signaling and adhesion mechanisms of contactin proteins as required for maintaining specific neuronal contacts and directing wiring between neuronal cells.