Journal article
Identification of tau protein regions required for process formation in PC12 cells
Journal of cell science, Vol.107 (12), pp.3403-3412
12/1994
DOI: 10.1242/jcs.107.12.3403
PMID: 7706394
Abstract
Tau is a neuronal microtubule-associated protein that is required for the development and maintenance of neuronal cell polarity. It promotes microtubule assembly in vitro and we have recently reported that a specific tau region, which spans amino acid residues 154-172 of human fetal tau, is not required for growth of existing microtubules, but is required for nucleation of new microtubules. These residues also confer stronger microtubule binding activity in 3T3 cells. The aim of this study was to investigate the functional organization of tau in relation to its role in promoting process formation in a neuronal model system. We transfected undifferentiated PC12 cells with vectors expressing tau fragments and treated the expressing cells with cytochalasin B to allow process extension. We found that deletion of amino acid residues 154-172 greatly reduced the percentage of transfected cells bearing processes compared to that of cells transfected with full-length tau or with an amino-terminally deleted tau fragment containing residues 154-172. These differences do not appear to result from a quantitative difference in protein expression, as shown by immunoblot analysis of transfected cells. We also observed that while the presence of tau fragments increases acetylation of microtubules, the pattern of acetylation in cells transfected with the fragment missing residues 154-172 is less extensive, suggesting that it does not result in the same level of stabilization as the longer tau fragments. Taxol promoted process outgrowth in cells treated with cytochalasin and restored process outgrowth to cells transfected with the tau fragment lacking this activity. Therefore, process formation involves primarily the stabilization and nucleation of microtubules. We conclude that the residues necessary for conferring microtubule nucleation activity of tau in vitro are important for process formation in vivo. It is likely that these residues influence the binding affinity and therefore the stabilization activity of tau.
Details
- Title: Subtitle
- Identification of tau protein regions required for process formation in PC12 cells
- Creators
- J G Léger - Center for Neurologic Diseases, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115R BrandtG Lee
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.107 (12), pp.3403-3412
- Publisher
- England
- DOI
- 10.1242/jcs.107.12.3403
- PMID
- 7706394
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Grant note
- AG07911 / NIA NIH HHS
- Language
- English
- Date published
- 12/1994
- Academic Unit
- Iowa Neuroscience Institute; Immunology; Internal Medicine
- Record Identifier
- 9984065376702771
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