MICROTUBULES ARE INVOLVED IN THE LOCALIZATION OF TAU-MESSENGER-RNA INPRIMARY NEURONAL CELL-CULTURES

Citation
P. Litman et al., MICROTUBULES ARE INVOLVED IN THE LOCALIZATION OF TAU-MESSENGER-RNA INPRIMARY NEURONAL CELL-CULTURES, Neuron, 13(6), 1994, pp. 1463-1474
Citations number
61
Categorie Soggetti
Neurosciences
Journal title
NeuronACNP
ISSN journal
08966273
Volume
13
Issue
6
Year of publication
1994
Pages
1463 - 1474
Database
ISI
SICI code
0896-6273(1994)13:6<1463:MAIITL>2.0.ZU;2-C
Abstract
Subcellular localization of neuronal mRNAs contributes to the developm ent of identifiable microdomains. In differentiated neurons, tau mRNA is localized in the cell body and the proximal portion of the axon, an d MAP2 mRNA is localized in the cell body and dendrites, whereas tubul in mRNA is restricted to the cell body. To investigate the mechanism(s ) leading to segregation of mictrotubule-associated protein mRNA, we e xamined the role of the cytoskeleton in this process. Detergent extrac tion of primary neuronal cells in culture followed by in situ hybridiz ation analysis demonstrated that tau mRNA remains bound to cytoskeleto n of the treated cells. In addition, biochemical fractionation showed that tau and MAP2 mRNAs are preferentially associated with the fractio n of assembled microtubules. In contrast, mRNAs restricted to the neur onal cell body, such as those of tubulin, the 68 kDa neurofilament, an d mouse GAPDH, are preferentially found in the supernatant. Using cyto skeletal inhibitors, we demonstrate that tau mRNA is associated with t he microtubule system, and not with the actin filaments, thus supporti ng the hypothesis that the mechanism of mRNA localization is a multist ep pathway in which the microtubules play a crucial role.