title: Sense and antisense transfection analysis of tau function: tau influences net microtubule assembly, neurite outgrowth and neuritic stability.
abstract: Microtubules are fundamental elements participating in many aspects of cell behavior and maintenance, yet the factors regulating microtubule behavior in vivo remain poorly understood. Employing the nerve growth factor (NGF)-responsive cell line, PC12, we have used sense and antisense DNA transfection strategies to examine the role of the microtubule-associated protein (MAP) tau in several aspects of neuronal cell behavior. Stable transfectants over-expressing tau accumulate more microtubule mass and extend neurites more rapidly than control cells, while transfectants under-expressing tau exhibit reduced microtubule levels and slower neurite outgrowth. Further, tau over-expressing cells are markedly more resistant to nocodazole-induced neuritic degeneration when compared to wild-type or tau under-expressing cells. These observations provide direct support for the model that tau is capable of influencing: (i) net microtubule assembly, (ii) the rate of neurite elongation and (iii) neuritic stability. These capabilities suggest that tau plays crucial roles in the development and maintenance of neuronal cells.
authors.affiliation: Department of Biological Sciences, University of California, Santa Barbara 93106.
authors.forename: B
authors.initials: B
authors.lastname: Esmaeli-Azad
authors.forename: J H
authors.initials: JH
authors.lastname: McCarty
authors.forename: S C
authors.initials: SC
authors.lastname: Feinstein
mesh_terms: D000818:Animals; D016373:DNA, Antisense / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure*; D015739:Nocodazole / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects / Q000648:ultrastructure; D016372:RNA, Antisense / Q000096:biosynthesis; D051381:Rats; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D016373:DNA, Antisense; D018076:DNA, Complementary; D009414:Nerve Growth Factors; D016372:RNA, Antisense; D014404:Tubulin; D016875:tau Proteins; D015739:Nocodazole