Developmental regulation and PKC dependence of Alzheimer's-type tau phosphorylations in cultured fetal rat hippocampal neurons

Colin K. Combs, Paul D. Coleman, M. Kerry O'Banion

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Attempts to describe a mechanism of neurofibrillary tangle formation often focus on site specific phosphorylations of tau protein. These have typically been described in both Alzheimer's disease and developing brains. Therefore, study of the developmental regulation of Alzheimer epitope tau phosphorylations may help explain their persistence or recurrence during Alzheimer's disease. Using fetal rat hippocampal cultures, we report a spatial and temporal expression of tau phosphorylation during neuronal differentiation. We have examined phosphorylation at the epitopes recognized by monoclonal antibodies, PHF-1 and Tau 1. Tau was highly phosphorylated at the PHF-1 epitope at all culture ages examined using both immunohistochemical staining and Western blots. Tau was heavily phosphorylated at the Tau 1 epitope only in older cultures. The populations of tau recognized by the two antibodies also exhibited different solubilities, suggesting different microtubule binding behaviors: tau phosphorylated at PHF-1 was retained in axons following solubilization whereas Tau 1 immunoreactive tau was not retained in any cell compartment. Finally, in this culture system, maintenance of phosphorylation at the PHF-1 epitope, but not the Tau 1 epitope, require protein kinase C activity. These results indicate unique regulatory mechanisms and roles for each of these phosphorylated tau epitopes.

Original languageEnglish (US)
Pages (from-to)143-158
Number of pages16
JournalDevelopmental Brain Research
Volume107
Issue number1
DOIs
StatePublished - Apr 17 1998
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Microtubule associated proteins
  • Neuronal culture
  • PHF-1
  • Phosphorylation
  • Tau 1

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

Fingerprint Dive into the research topics of 'Developmental regulation and PKC dependence of Alzheimer's-type tau phosphorylations in cultured fetal rat hippocampal neurons'. Together they form a unique fingerprint.

Cite this