Visualization of translated tau protein in the axons of neuronal P19 cells and characterization of tau RNP granules
Abstract
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.
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HuD is localized to granules, along with other proteins such as KIF3A and SMN, within the cytoplasm and neurites.
“Closer inspection of intraneuronal compartments revealed that HuD is localized to granules, along with other proteins, such as kinesin-like protein (KIF3A) and survival of motoneuron (SMN), within the cytoplasm and neurites (Aronov et al. 2002; Smith et al. 2004; Tiruchinapalli et al. 2008a,b; Hubers et al. 2010; Akten et al. 2011; Fallini et al. 2012b).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Aronov et al. 2002
In developing neurons, HuD is found in growth cones of extending neurites, while in mature neurons it is present in axons and dendrites, including at the pre- and post-neurite terminals.
“In developing neurons, HuD is found in growth cones of extending neurites, while in mature neurons it is present in axons and dendrites, including at the pre- and post-neurite terminals, respectively (Aranda-Abreu et al. 1999; Aronov et al. 2002).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Aronov et al. 2002
HuD interacts with a host of mRNP components involved in transport and translation in the cytoplasm and neurites, such as KIF3A, IMP-1, SMN, PABP, eEF4E, and MAP1B.
“Co-IP and immunocytochemistry experiments revealed that HuD interacts with a host of mRNP components involved in transport and translation in the cytoplasm and neurites such as the motor protein KIF3A (Aronov et al. 2002), IGF-II mRNA binding protein 1 (IMP-1) (Atlas et al. 2004, 2007), survival of motor neuron (SMN) (Hubers et al. 2010; Akten et al. 2011; Fallini et al. 2011), poly(A) binding”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Aronov et al. 2002
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- Authors
- Aronov, S., Aranda, G., Behar, L., & Ginzburg, I.
- Affiliations
- Weizmann Institute of Science (IL)
- ORCID
- Aronov, Stella
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2002-10-01
- Volume
- 115
- Issue
- 19
- Pages
- 3817-3827
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2119374350
- Cited by
- 112
- References
- 0
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 8 · 2019: 5 · 2018: 3 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 6 · 2012: 9
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- tau protein, KIF3A, kinesin motor protein, anterograde transport, axonal growth cones, axonal protein synthesis, 3' untranslated region, neurite retraction
- MeSH terms
- ELAV-Like Protein 4, Animals, Axonal Transport, Cell Differentiation, Cells, Cultured, Central Nervous System, Cytoplasmic Granules, Humans, Luminescent Proteins, Nerve Tissue Proteins, Recombinant Fusion Proteins, Ribonucleoproteins, RNA, Messenger, Protein Biosynthesis, Tubulin, Neoplastic Stem Cells, Antisense Elements (Genetics), Kinesins, RNA-Binding Proteins, tau Proteins, Growth Cones, Protein Transport, Green Fluorescent Proteins, ELAV Proteins
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