This project is designed to explore spectrin and associated cytoskeletal proteins in regard to the structure and function of the developing nervous system. During the first 2 years of this grant we have discovered two subtypes of brain spectrin (240/235) and (240/235E) in the mammalian brain, and localized these isoforms with immunocytochemistry and immunoelectron microscopy. Brain spectrin (240/235) is located primarily in the axons and presynaptic terminals of neurons. Brain spectrin (240/235E) is found in the cell bodies, dendrites, and postsynaptic terminals of neurons, as well as in certain glial cell types. The ontogeny of these spectrin subtypes was explored in immunoautoradiography experiments, and closely examined with immunocytochemical procedures. Each spectrin subtype had a distinct pattern of expression and distribution in the developing nervous system. In this application we describe experiments which are designed to give us a better understanding of brain spectrin subtypes and associated spectrin binding proteins in regard to the development of the mammalian nervous system.
The aims of this proposal are: (1) Determine the location and distribution of brain spectrin subtypes in the developing mouse brain using immunoelectron microscopy. (2) Quantitate brain spectrin (240/235E) with quantitative immunodot assay. (3) Define whether there are structural changes in the isoforms of spectrin during development using immunoprecipitation and peptide mapping techniques. (4) Examine whether there are two ankyrin (syndein) subtypes in the mammalian brain utilizing immunoblots and immunohistochemistry. (5) Determine the ontogeny of ankyrin subtypes in the brain with immunoblots, immunodots, immunohistochemistry, and immunoelectron microscopy. (6) Examine the expression of amelin during mammalian brain development employing the techniques outlined in (5). The studies proposed constitute important and novel inquiries into the functional significance of spectrin-like proteins in the binding proteins in neural cells and tissues. This investigation is part of an ongoing program in cellular and molecular neurobiology which seeks to understand the process of normal and abnormal brain development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021246-05
Application #
3402189
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1984-07-01
Project End
1992-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Zimmer, W E; Ma, Y; Zagon, I S et al. (1992) Developmental expression of brain beta-spectrin isoform messenger RNAs. Brain Res 594:75-83
Isayama, T; Goodman, S R; Zagon, I S (1991) Spectrin isoforms in the mammalian retina. J Neurosci 11:3531-8
Goodman, S R; Lopresti, L L; Riederer, B M et al. (1989) Brain spectrin(240/235A): a novel astrocyte specific spectrin isoform. Brain Res Bull 23:311-6
Zagon, I S; Goodman, S R (1989) Absence of brain spectrin(240/235) in dendrites of mammalian brain. Brain Res Bull 23:19-24
Riederer, B M; Lopresti, L L; Krebs, K E et al. (1988) Brain spectrin(240/235) and brain spectrin(240/235E): conservation of structure and location within mammalian neural tissue. Brain Res Bull 21:607-16
Hess, G D; Zagon, I S (1988) Endogenous opioid systems and neural development: ultrastructural studies in the cerebellar cortex of infant and weanling rats. Brain Res Bull 20:473-8
Zagon, I S (1987) Endogenous opioids, opioid receptors, and neuronal development. NIDA Res Monogr 78:61-71
Zagon, I S; McLaughlin, P J (1987) The location and orientation of mitotic figures during histogenesis of the rat cerebellar cortex. Brain Res Bull 18:325-36
Krebs, K E; Zagon, I S; Sihag, R et al. (1987) Brain protein 4.1 subtypes: a working hypothesis. Bioessays 6:274-9
Krebs, K E; Prouty, S M; Zagon, I S et al. (1987) Structural and functional relationship of red blood cell protein 4.1 to synapsin I. Am J Physiol 253:C500-5

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