A long term objective of this laboratory is to understand the structure, location and functions of spectrin isoforms within mammalian brain. In the last grant period we identified three brain spectrin isoforms: [1] brain spectrin(240/235) which is found in axons and neuronal soma, [2] brain spectrin(240/235E) which is an erythroid-like isoform found in neuronal soma and dendrites as well as oligodendrocytes, and [3] brain spectrin(240/235A) which is located exclusively in astrocyte soma and processes. We have also identified two beta spectrin mRNAs of 9 Kb and 11 Kb size in mouse brain. Through cloning and sequencing of cDNA, we have obtained greater than 50% of the deduced sequence of the 9 Kb mRNA (which we believe to be the beta subunit of 240/235E). During the next grant period, we will complete the sequence of the 9 Kb and 11 Kb transcripts; identify the spectrin isoform specificity for binding of synaptic vesicles (synapsin I) and ankyrin, utilizing bacterially expressed segments of the 9 Kb and 11 Kb beta spectrins; identify the minimal binding sequence and essential amino acids for binding synaptic vesicles and ankyrin by deletion mutagenesis and site specific mutagenesis of beta spectrin cDNA, and determine whether the interaction of synaptic vesicles with brain spectrin via synapsin I is regulated by Ca2+ and calmodulin (new specific aim). As small spherical synaptic vesicles appear to be attached to the active zone of the presynaptic plasma membrane by spectrin, the newly added specific aim is essential to our understanding of Ca2+ regulated exocytosis of neurotransmitter within the nerve terminal. The Principal Investigator and his coworkers published 60 scientific articles and abstracts on brain spectrin and related molecules during the previous grant period (1986- 1991).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS019357-10A1
Application #
3399420
Study Section
Neurology C Study Section (NEUC)
Project Start
1989-01-01
Project End
1995-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
10
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of South Alabama
Department
Type
Schools of Medicine
DUNS #
City
Mobile
State
AL
Country
United States
Zip Code
36688
Goodman, S R; Zimmer, W E; Clark, M B et al. (1995) Brain spectrin: of mice and men. Brain Res Bull 36:593-606
Lengeling, A; Zimmer, W E; Goodman, S R et al. (1994) Exclusion of two candidate genes, Spnb-2 and Dcd, for the wobbler spinal muscular atrophy gene on proximal mouse chromosome 11. Mamm Genome 5:163-6
Clark, M B; Ma, Y; Bloom, M L et al. (1994) Brain alpha erythroid spectrin: identification, compartmentalization, and beta spectrin associations. Brain Res 663:223-36
Ma, Y; Zimmer, W E; Riederer, B M et al. (1993) The complete amino acid sequence for brain beta spectrin (beta fodrin): relationship to globin sequences. Brain Res Mol Brain Res 18:87-99
Bloom, M L; Lee, B K; Birkenmeier, C S et al. (1992) Brain beta spectrin isoform 235 (Spnb-2) maps to mouse chromosome 11. Mamm Genome 3:293-5
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
Zimmer, W E; Zagon, I S; Casoria, L A et al. (1992) Identification of an amelin isoform located in axons. Brain Res 582:94-100
Zimmer, W E; Ma, Y P; Goodman, S R (1991) Identification of a mouse brain beta-spectrin cDNA and distribution of its mRNA in adult tissues. Brain Res Bull 27:187-93
Sikorski, A F; Goodman, S R (1991) The effect of synapsin I phosphorylation upon binding of synaptic vesicles to spectrin. Brain Res Bull 27:195-8
Isayama, T; Goodman, S R; Zagon, I S (1991) Spectrin isoforms in the mammalian retina. J Neurosci 11:3531-8

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