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Dissertation
Regulation of gene expression, protein phosphorylation and axonal transport of microtubule-associated protein 1B (MAP1B) in developing and regenerating DRG neurons
Doctor of Philosophy (Ph.D.), Medical College of Pennsylvania and Hahnemann University
Apr 1999
DOI:
https://doi.org/10.17918/00008054
Abstract
MAP1B is a major cytoskeletal protein in growing axons and is highly regulated during brain development. The phosphorylated isoform, MAP1B-P, is preferentially localized in axons and concentrated in the distal end of growing axons. We have analyzed the expression of MAP1B and its mRNA by Western blots and RNase Protection Assay and demonstrated that the levels of both the protein and mRNA remained relatively high at all stages of development including adult DRG. We found that following axotomy of the sciatic nerve, there was a small decrease in levels of MAP1B and its mRNA; however, the appearance of regenerating axons in the distal stump was concurrent with an intense expression of MAP1B in the growing axons indicating that MAP1B plays a role in nerve regeneration. In contrast, the levels of MAP1B-P decreased dramatically in the distal stump and were not present in the regenerating axons. These results indicate that MAP1B-P may not be essential for axonal growth during nerve regeneration, underscoring the differences between axonal growth in development and regeneration. Further analysis demonstrated that the expression of MAP1B was also induced in activated Schwann cells following nerve lesion, suggesting that MAP1B may be necessary for the morphological changes associated with the formation of processes prior to their differentiation into myelin-forming cells. The expression of MAP1B was confirmed in cultured Schwann cells, but these cells express only a restricted population of phosphorylated MAP1B isoforms. Kinetic analysis of MAP1B transport in axons was carried out by injection of radiolabeled amino acids into DRG followed by autoradiography of the sciatic nerve. This analysis showed that two radiolabeled MAP1B isoforms (band 1 and band 2) were transported at different rates. Band 1 moved as a coherent wave at a velocity of 7-9 mm/day, distinct from slow components SCa (1.5 mm/day) and SCb (4 mm/day). In contrast, the transport profile of band 2 was complex and contained components moving with both SCa and SCb. The relative fast transport of the band 1 MAP1B defines a unique component that we termed SCc and may account for the concentration of MAP1B in the distal end of growing axons.
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Details
- Title
- Regulation of gene expression, protein phosphorylation and axonal transport of microtubule-associated protein 1B (MAP1B) in developing and regenerating DRG neurons
- Creators
- Dongling Ma
- Contributors
- Thomas B. Shea (Advisor) - Drexel University, Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Awarding Institution
- Medical College of Pennsylvania and Hahnemann University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Medical College of Pennsylvania and Hahnemann University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 324 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Medicine (1993-1996, 1998-2002); Medical College of Pennsylvania and Hahnemann University (1993-1996, 1998-2002)
- Other Identifier
- 991021889010804721