Although we know a great deal about compact myelin, its component proteins and how they are assembled, our knowledge of the non-compacted membranes and the cytoplasmic channels they enclose is exceedingly limited. These channels are the """"""""vital zones"""""""" of the myelinating cell, where molecular interchanges take place with the external transduction. One structure formed at the close apposition of the paranodal loops of glial membrane is the axoglial junction, an extraordinary, complicated structure whose component proteins, with a few exceptions, remain unknown. How this junction's protein components interact to generate the ladder-like cleft structure visualized by thin section microscopy is a fascinating problem, whose resolution will yield an understanding of how the myelinating cell plasma membrane is attached to the axonal surface. As a related problem, the cytoplasmic channels immediately emanating from the glial side of the CNS axoglial junctional ribbon are almost certainly held in register, s they are in the PNS, by adhesion molecules, possible of the cadherin super family. Our long range goal is to understand the biology of the adhesion molecules that mediate membrane interactions in the non-compact regions of myelin, and in particular at the paranodes. This is an application to implement a cell fractionation scheme that we have developed to isolate these membrane elements from the CNS white matter with high purity, identify with the greatest specificity and highest sensitivity the component proteins using the state-of-the-art mass spectrometry, and then study the adhesive interactions between these proteins at the membrane surfaces on which they are displayed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS040560-01
Application #
6197616
Study Section
Special Emphasis Panel (ZRG1-MDCN-2 (01))
Program Officer
Behar, Toby
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
1
Fiscal Year
2000
Total Cost
$339,000
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Biochemistry
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
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