TY - JOUR
T1 - Visualization of translated tau protein in the axons of neuronal P19 cells and characterization of tau RNP granules
AU - Aronov, Stella
AU - Aranda, Gonzalo
AU - Behar, Leah
AU - Ginzburg, Irith
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Localization of tau mRNA to the axon requires the axonal localization cis signal (ALS), which is located within the 3′ untranslated region, and trans-acting binding proteins, which are part of the observed granular structures in neuronal cells. In this study, using both biochemical and morphological methods, we show that the granules contain tau mRNA, HuD RNA-binding protein, which stabilizes mRNA, and KIF3A, a member of the kinesin microtubule-associated motor protein family involved in anterograde transport. The granules are detected along the axon and accumulate in the growth cone. Inhibition of KIF3A expression caused neurite retraction and inhibited tau mRNA axonal targeting. Taken together, these results suggest that HuD and KIF3A proteins are present in the tau mRNA axonal granules and suggest an additional function for the kinesin motor family in the microtubule-dependent translocation of RNA granules. Localized tau-GFP expression was blocked by a protein synthesis inhibitor, and upon release from inhibition, nascent tau-GFP 'hot spots' were directly observed in the axon and growth cones. These observations are consistent with local protein synthesis in the axon resulting from the transported tau mRNA.
AB - Localization of tau mRNA to the axon requires the axonal localization cis signal (ALS), which is located within the 3′ untranslated region, and trans-acting binding proteins, which are part of the observed granular structures in neuronal cells. In this study, using both biochemical and morphological methods, we show that the granules contain tau mRNA, HuD RNA-binding protein, which stabilizes mRNA, and KIF3A, a member of the kinesin microtubule-associated motor protein family involved in anterograde transport. The granules are detected along the axon and accumulate in the growth cone. Inhibition of KIF3A expression caused neurite retraction and inhibited tau mRNA axonal targeting. Taken together, these results suggest that HuD and KIF3A proteins are present in the tau mRNA axonal granules and suggest an additional function for the kinesin motor family in the microtubule-dependent translocation of RNA granules. Localized tau-GFP expression was blocked by a protein synthesis inhibitor, and upon release from inhibition, nascent tau-GFP 'hot spots' were directly observed in the axon and growth cones. These observations are consistent with local protein synthesis in the axon resulting from the transported tau mRNA.
KW - Axonal local translation
KW - HuD
KW - KIF3A
KW - P19 EC cells
KW - RNA axonal localization
KW - RNP granules
KW - Tau mRNA
KW - Tau protein
UR - http://www.scopus.com/inward/record.url?scp=0036798495&partnerID=8YFLogxK
U2 - 10.1242/jcs.00058
DO - 10.1242/jcs.00058
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C2 - 12235292
AN - SCOPUS:0036798495
SN - 0021-9533
VL - 115
SP - 3817
EP - 3827
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 19
ER -