Microtubule-associated proteins (MAPs) have previously been shown to interact primarily with microtubules both in vitro and in situ. However, we have recently documented the association of one MAP, tau, with ribosomes in neural cells as well as with microtubules. Additionally, analysis of the bovine tau gene sequence indicates the existence of, as yet, undescribed isoforms of this protein encoded in EXON 14 that may impart DNA binding properties to tau. We have shown that both tau and a MAPlB-like protein localize in nucleoli in primate cells in culture (see Section C). Hence, MAP1B and tau appear to be multifunctional molecules that are involved in nuclear processes as well as in microtubule biology. We hypothesize that targeting of these MAPs to either microtubules in specific neural compartments in the brain or to the nucleus in rapidly dividing cells involves transcriptional and/or translational modifications that uniquely adapt a particular MAP species to its eventual segregation and function. This hypothesis will be tested by (1) defining chemical and functional differences between nuclear and microtubule-derived tau and MAP1B, (2) elucidating the biology of nuclear tau and the MAPlB-like polypeptide, and by (3) determining whether the nuclear tau polypeptides represent unique, DNA-binding isoforms of tau.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG006969-08
Application #
2049647
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1987-06-01
Project End
1995-03-31
Budget Start
1994-04-15
Budget End
1995-03-31
Support Year
8
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Applied Neurosolutions, Inc.
Department
Type
DUNS #
City
Vernon Hills
State
IL
Country
United States
Zip Code
60061
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Brady, R M; Zinkowski, R P; Binder, L I (1995) Presence of tau in isolated nuclei from human brain. Neurobiol Aging 16:479-86
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Wang, Y; Loomis, P A; Zinkowski, R P et al. (1993) A novel tau transcript in cultured human neuroblastoma cells expressing nuclear tau. J Cell Biol 121:257-67
Brown, K D; Zinkowski, R P; Hays, S E et al. (1993) Actin-binding protein is a component of bovine erythrocytes. Cell Motil Cytoskeleton 24:100-8
Brown, K D; Binder, L I (1993) Expression of the cytoskeletal-associated protein filamin in adult rat organs. Exp Cell Res 209:325-32
Brown, K D; Binder, L I (1992) Identification of the intermediate filament-associated protein gyronemin as filamin. Implications for a novel mechanism of cytoskeletal interaction. J Cell Sci 102 ( Pt 1):19-30
Kim, H (1991) Depletion of acetylated alpha-tubulin during microtubule purification from bovine brain gray and white matter regions. J Neurosci Res 30:172-82

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