The molecular organization and function of paranodal septate junctions Public Deposited

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  • March 22, 2019
Creator
  • Garcia-Fresco, German P.
    • Affiliation: School of Medicine, UNC Neuroscience Center, Neuroscience Curriculum
Abstract
  • Close communication between axons and glial cells is required and necessary for maturation, organization and maintenance of the nervous system. The axon provides signals to promote differentiation, survival and proliferation of both oligodendrocytes and Schwann cells in the central and peripheral nervous systems respectively, while providing instructions to regulate myelin thickness. Conversely, glial cells provide reciprocal signals that regulate and control axonal mechanisms such as axonal thickness and transport. The combined efforts of glial and axonal signals result in a mature myelinated fiber that has a structural organization optimal for a maximum conduction velocity. One characteristic feature of myelinated fibers is their ability to organize specialized domains with distinctive molecular and structural characteristics. The myelinated domains include the node of Ranvier, the paranodal junction, the juxtaparanodal junction and the internodal region. This domain organization is a result of the fine bi-directional communication between the axon and the overlying glial cell. The paranodal axo-glial junction is a complex of proteins including: NCP1, Contactin (CN), Neurofascin 155 (NF155) and band 4.1B. NF155 is expressed by the overlying glial cell while the others are clustered on the axonal membrane. All proteins are necessary for the maintenance and establishment of the paranodal domain and provide a link to the axonal cytoskeleton. We and others have previously characterized two knockout mice (NCP1 and CGT) that display several signs of cerebellar deficits, including abnormal motor coordination, tremors at rest and ataxia. These knockouts share the same phenotypes one of which is their inability to form paranodal junctions properly. Interestingly NCP1 is an axonal protein and CGT is a glial protein suggesting a common mechanism of action by both cell types and the importance of axo-glial interactions in proper axonal development and organization. The goal of this project is to further understand the role, molecular composition and organization of axo-glial junctions in vertebrate systems, in particular the paranodal junction of myelinated nerve fibers. We will use these two knockout mouse model systems to identify new key components that play a role in establishing a link between the axon and glial cells.
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  • In Copyright
Advisor
  • Bhat, Manzoor A.
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Open access
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