Fragile X mental retardation protein induces synapse loss through acute postsynaptic translational regulation
Abstract
Fragile X syndrome, as well as other forms of mental retardation and autism, is associated with altered dendritic spine number and structure. Fragile X syndrome is caused by loss-of-function mutations in Fragile X mental retardation protein (FMRP), an RNA-binding protein that regulates protein synthesis in vivo . It is unknown whether FMRP plays a direct, cell-autonomous role in regulation of synapse number, function, or maturation. Here, we report that acute postsynaptic expression of FMRP in Fmr1 knock-out (KO) neurons results in a decrease in the number of functional and structural synapses without an effect on their synaptic strength or maturational state. Similarly, neurons endogenously expressing FMRP (wild-type) have fewer synapses than neighboring Fmr1 KO neurons. An intact K homology domain 2 (KH2) RNA-binding domain and dephosphorylation of FMRP at S500 were required for the effects of FMRP on synapse number, indicating that FMRP interaction with RNA and translating polyribosomes leads to synapse loss.
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Loss of FMRP enhances NMDAR function in young mice but not in adult mice.
“Loss of FMRP enhances NMDAR function in young (Pfeiffer and Huber, 2007; Pilpel et al., 2008), but not in adult mice (Pilpel et al., 2008; Zhao et al., 2005).”
From Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132 (2010) · cites this paper as Pfeiffer and Huber, 2007
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- Authors
- Pfeiffer, B. E., & Huber, K. M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-03-21
- Volume
- 27
- Issue
- 12
- Pages
- 3120-3130
- ISSN
- 0270-6474
- 1529-2401
- Cited by
- 154
- References
- 6
- Language
- en
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