Distinct Role of Long 3′UTR BDNF mRNA in Spine Morphology and Synaptic Plasticity in Hippocampal Neurons

By J. An, Kusumika Gharami, Guey‐Ying Liao, N. Woo, A. Lau, Filip Vanevski, E. Torre, K. R. Jones, Yue Feng, B. Lu and 1 more. Cell, 2008

697 citations recorded by the source corpus.

SUMMARY The brain produces two brain-derived neurotrophic factor (BDNF) transcripts, with either short or long 3′ untranslated regions (3′UTR). The physiological significance of the two forms of mRNAs encoding the same protein is unknown. Here we show that the short and long 3′UTR BDNF mRNAs are involved in different cellular functions. The short 3′UTR mRNAs are restricted to somata whereas the long 3′UTR mRNAs are also localized in dendrites. In a mouse mutant where the long 3′UTR is truncated, dendritic targeting of BDNF mRNAs is impaired. There is little BDNF in hippocampal dendrites despite normal levels of total BDNF protein. This mutant exhibits deficits in pruning and enlargement of dendritic spines, as well as selective impairment in long-term potentiation in dendrites, but not somata, of hippocampal neurons. These results provide insights into local and dendritic actions of BDNF and reveal a mechanism for differential regulation of subcellular functions of proteins.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1703bd2d28b4c443fb5019da12f8d37f74ac6ca3

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. B. Lu
2. C. Duarte
3. Graciano Leal
4. Diogo Comprido
5. B. Hempstead
6. Michael E. Greenberg
7. Baoji Xu
8. Mauro Costa-Mattioli

In Developmental Neuroscience

1. B. Hempstead
2. B. Lu
3. Michael E. Greenberg
4. C. Duarte
5. Graciano Leal
6. Diogo Comprido
7. Baoji Xu

In Molecular Biology

1. Mauro Costa-Mattioli
2. E. Klann
3. B. Lu
4. Wayne S. Sossin
5. Paul L. Greer
6. C. Duarte
7. Graciano Leal
8. Diogo Comprido

Citations in the corpus

• Translational control of long-lasting synaptic plasticity and memory. (2009, background): “…mutations that abrogate transport of BDNF mRNA to dendrites cause a deficit in pruning and enlargement of dendritic spines, suggesting that the specific role of BDNF in dendrites is to regulate spine density and the ability to induce protein synthesisindependent forms of LTP (An et al., 2008).”
• BDNF-induced local protein synthesis and synaptic plasticity. (2014, positive): “Deficits in dendritic synthesis of BDNF also lead to the selective impairment of LTP in dendrites (An et al., 2008).”
• From synapse to nucleus: calcium-dependent gene transcription in the control of synapse development and function. (2008, background): “Furthermore, mice that lack the long 30 UTR have impaired dendritic spine morphogenesis as well as defects in synaptic plasticity (An et al., 2008).”
• New insights in the biology of BDNF synthesis and release: implications in CNS function (2009, positive): “Through the use of alternative promoters, splicing and polyadenylation sites, at least 18 transcripts can be produced, but remarkably, each encodes an identical initial BDNF protein product.”