Two experimental animal models of neuropathy permit the in vivo assessment of alterations in Schwann cell metabolism that occur during the presence and absence of myelin assembly. The crush-injured, adult rat sciatic nerve permits the analysis of Schwann cell metabolism during active myelin assembly whereas the permanently transected nerve permits analysis of Schwann cells in the absence of myelin assembly. The purpose of this grant application is to determine the biosynthetic control mechanisms in the post-translational processing of the major myelin protein (PO) expressed by Schwann cells in these two models of neuropathy. This will be compared to the processing events in the normal adult nerve, as well as the nerve during development. Processing events that will be investigated will include glycosylation, phosphorylation, sulfation, and acylation. In addition, by directly comparing these events, using the appropriate radioactive precursor, it should be possible to assess the sequence of these post translational modifications. Scientific methods to be employed include 1) radioactive precursor incorporation into PO after in vitro incubation gradient electrophoresis as identified by fluorography and autoradiography; c) serial lectin affinity chromatography coupled with endoglycosidase and exoglycosidase digestion to determine the precise oligosaccharide structure calibrated gel filtration and high performance liquid chromatography. The post- translational modification of proteins is an important processing event which governs the appropriate targeting of proteins to their often uniquely determined by the protein modifications. Little information is available concerning the mechanism which regulate these post-translational control mechanisms will foster future research concerning potential abnormal protein processing resulting in defective intra- or extracellular targeting and subsequent disruption of cellular communication.

Agency
National Science Foundation (NSF)
Institute
Division of Integrative Organismal Systems (IOS)
Application #
8706703
Program Officer
Stacy Springer
Project Start
Project End
Budget Start
1988-01-15
Budget End
1991-06-30
Support Year
Fiscal Year
1987
Total Cost
$134,100
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905