Gem GTPase and Tau: Morphological changes induced by Gem GTpase in CHO cells are antagonized by tau

Fumitaka Oyama, Svetlana Kotliarova, Akihiro Harada, Mamoru Ito, Haruko Miyazaki, Yoshito Ueyama, Nobutaka Hirokawa, Nobuyuki Nukina, Yasuo Ihara

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

A series of observations have indicated that tau, one of the major microtubule-associated proteins, is involved in neuronal cell morphogenesis and axonal maintenance. Tau is also the major component of paired helical filaments found in brains affected by Alzheimer's disease. To explore an as yet unidentified role of tau in vivo, ∼11,000 mRNAs were profiled from tau-deficient mouse brains and compared with those from control brains at the same ages. The expression of Gem GTPase, a small GTP-binding protein of the ras superfamily, was significantly increased in the brains of tau-deficient mice at 8 weeks of age. Because Gem GTPase is a negative regulator of the Rho-Rho kinase pathway for cytoskeletal organization, this protein was transiently overexpressed in Chinese hamster ovary cells that do not express tau. Overexpression of Gem GTPase induced a marked elongation of Chinese hamster ovary cells, and simultaneous expression of tau eliminated this effect, although tau did not bind directly to Gem GTPase. This anti-elongation activity of tau was attributed to its microtubule-binding domain, and homologous domains of microtubule-associated proteins 2 and 4 exhibited similar antagonistic activities. Taken together, the present results indicate that the level of Gem GTPase and its cell elongation activity are modulated by tau and suggest that tau may be involved in a Gem GTPase-mediated signal transduction pathway.

Original languageEnglish
Pages (from-to)27272-27277
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number26
DOIs
Publication statusPublished - Jun 25 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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