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Differential translation and fragile X syndrome
Abstract
Fragile X syndrome (FXS) is caused by the transcriptional silencing of the Fmr1 gene, which encodes a protein (FMRP) that can act as a translational suppressor in dendrites, and is characterized by a preponderance of abnormally long, thin and tortuous dendritic spines. According to a current theory of FXS, the loss of FMRP expression leads to an exaggeration of translation responses linked to group I metabotropic glutamate receptors. Such responses are involved in the consolidation of a form of long‐term depression that is enhanced in Fmr1 knockout mice and in the elongation of dendritic spines, resembling synaptic phenotypes over‐represented in fragile X brain. These observations place fragile X research at the heart of a long‐standing issue in neuroscience. The consolidation of memory, and several distinct forms of synaptic plasticity considered to be substrates of memory, requires mRNA translation and is associated with changes in spine morphology. A recent convergence of research on FXS and on the involvement of translation in various forms of synaptic plasticity has been very informative on this issue and on mechanisms underlying FXS. Evidence suggests a general relationship in which the receptors that induce distinct forms of efficacy change differentially regulate translation to produce unique spine shapes involved in their consolidation. We discuss several potential mechanisms for differential translation and the notion that FXS represents an exaggeration of one ‘channel’ in a set of translation‐dependent consolidation responses.
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“Excessive mTOR-dependent neuronal protein synthesis is also involved in other neurogenetic syndromes linked to mental retardation and autism[29](#R29),[30](#R30).”
From Reversal of learning deficits in a Tsc2+/− mouse model of tuberous sclerosis (2008) · cites this paper as [29]
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Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876 · cited 1×
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BackgroundAMPA Receptor Trafficking and Synaptic Plasticity
Malinow, R., & Malenka, R. C. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142758 · Cited by 2,588
Structural basis of long-term potentiation in single dendritic spines
Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. R., & Kasai, H. (2004) · Nature · doi:10.1038/nature02617 · Cited by 2,483
Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex
Trachtenberg, J. T., Chen, B. E., Knott, G. W., Feng, G., Sanes, J. R., Welker, E., & Svoboda, K. (2002) · Nature · doi:10.1038/nature01273 · Cited by 1,927
Synaptic tagging and long-term potentiation
Frey, U., & Morris, R. G. M. (1997) · Nature · doi:10.1038/385533a0 · Cited by 1,736 · cited 1×
“Evidence for a synaptic ‘tag’ directing new proteins, or local synthesis, to plastic synapses has emerged (Barco et al. 2002; Frey & Morris 1997; Steward & Worley 2001).”
BackgroundThe mGluR theory of fragile X mental retardation
Bear, M. F., Huber, K. M., & Warren, S. T. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.04.009 · Cited by 1,580
Matsuzaki, M., Ellis-Davies, G. C. R., Nemoto, T., Miyashita, Y., Iino, M., & Kasai, H. (2001) · Nature Neuroscience · doi:10.1038/nn736 · Cited by 1,563 · cited 1×
“Studies utilizing local 2-photon uncaging of glutamate indicate that spine geometry and synaptic strength are correlated: long, thin spines and filopodia have fewer functional AMPARs than short spines with larger heads (Matsuzaki et al. 2001).”
BackgroundRegulation of translation initiation by FRAP/mTOR
Gingras, A.-C., Raught, B., & Sonenberg, N. (2001) · Genes & Development · doi:10.1101/gad.887201 · Cited by 1,545
PSD-95 Involvement in Maturation of Excitatory Synapses
El-Husseini, A. E.-D., Schnell, E., Chetkovich, D. M., Nicoll, R. A., & Bredt, D. S. (2000) · Science · doi:10.1126/science.290.5495.1364 · Cited by 1,303
Long-term dendritic spine stability in the adult cortex
Grutzendler, J., Kasthuri, N., & Gan, W.-B. (2002) · Nature · doi:10.1038/nature01276 · Cited by 1,198
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Metadata
- Authors
- Vanderklish, P. W., & Edelman, G. M.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2005-04-06
- Volume
- 4
- Issue
- 6
- Pages
- 360-384
- ISSN
- 1601-1848
- 1601-183X
- Cited by
- 59
- References
- 32
- Language
- en
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