Molecular Principles of Nerve Conduction Along Myelinated Axons: Insights into Human Neuropathies

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Date: January 30, 2020
Time: 11:00 a.m. - 12:00 p.m.
Location: Scott Hall #2268 | Map
540 E. Canfield
Detroit, MI 48201
Category: Seminar

Manzoor A. Bhat, PhD
Professor and Chairman, Zachry Foundation Distinguished Chair in Neurosciences, Department of Cellular and Integrative Physiology, University of Texas Health Science Center, San Antonio 

“Molecular Principles of Nerve Conduction Along Myelinated Axons: Insights into Human Neuropathies”


Myelinated axons are organized into molecularly and functionally distinct domains defined by the presence of specific protein complexes that allow rapid saltatory action potential propagation. The paranodal domain contains the axo-glial junctions (AGJs) that are established by axonal Contactin-associated protein 1 (Cntnap1 or Caspr1), and Contactin and myelin/glial Neurofascin 155. The nodal domains (nodes of Ranvier) are organized by neuronal Neurofascin 186, voltage-gated sodium channels, and two cytoskeletal scaffolding proteins Ankyrin G and βIV Spectrin. In myelin-related diseases, this domain structure is compromised, leading to a decrease or loss of nerve conduction and muscle weakness. Our work demonstrated specific functions of the above proteins in the organization, maturation and maintenance of axonal domains. Importantly, recent identification of human CNTNAP1 mutations that are associated with severe AGJ and myelin defects further highlight the importance of AGJ proteins in nerve structure and function. While significant advances have been made regarding the organization of axonal domains; there still remain fundamental overarching questions related to AGJs and neuromuscular health: What impact do human mutations have on AGJ formation and physiological properties of axons? How does progressive disruption of axonal domains affect axons and the muscles they innervate? How does declining nerve activity change neuromuscular junctions (NMJs) and lead to muscle atrophy. Collectively, our studies are fundamentally advancing our understanding of how human AGJ- and myelin-related pathologies impact axonal and neuromuscular health; and may offer critical insights into the timelines of functional restoration and potential avenues for future therapeutic interventions for these devastating neuropathologies.


Suzanne Shaw




Current students, Faculty