Fragile X mental retardation protein is translated near synapses in response to neurotransmitter activation

Local translation of proteins in distal dendrites is thought to support synaptic structural plasticity. We have previously shown that metabotropic glutamate receptor (mGluR1) stimulation initiates a phosphorylation cascade, triggering rapid association of some mRNAs with translation machinery near synapses, and leading to protein synthesis. To determine the identity of these mRNAs, a cDNA library produced from distal nerve processes was used to screen synaptic polyribosome-associated mRNA. We identified mRNA for the fragile X mental retardation protein (FMRP) in these processes by use of synaptic subcellular fractions, termed synaptoneurosomes. We found that this mRNA associates with translational complexes in synaptoneurosomes within 1–2 min after mGluR1 stimulation of this preparation, and we observed increased expression of FMRP after mGluR1 stimulation. In addition, we found that FMRP is associated with polyribosomal complexes in these fractions. In vivo, we observed FMRP immunoreactivity in spines, dendrites, and somata of the developing rat brain, but not in nuclei or axons. We suggest that rapid production of FMRP near synapses in response to activation may be important for normal maturation of synaptic connections.

A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P

The absence of the fragile X mental retardation protein (FMRP), encoded by the FMR1 gene, is responsible for pathologic manifestations in the Fragile X Syndrome, the most frequent cause of inherited mental retardation. FMRP is an RNA-binding protein associated with polysomes as part of a messenger ribonucleoprotein (mRNP) complex. Although its function is poorly understood, various observations suggest a role in local protein translation at neuronal dendrites and in dendritic spine maturation. We present here the identification of CYFIP1/2 (Cytoplasmic FMRP Interacting Proteins) as FMRP interactors. CYFIP1/2 share 88% amino acid sequence identity and represent the two members in humans of a highly conserved protein family. Remarkably, whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P/2P, CYFIP1 interacts exclusively with FMRP. FMRP–CYFIP interaction involves the domain of FMRP also mediating homo- and heteromerization, thus suggesting a competition between interaction among the FXR proteins and interaction with CYFIP. CYFIP1/2 are proteins of unknown function, but CYFIP1 has recently been shown to interact with the small GTPase Rac1, which is implicated in development and maintenance of neuronal structures. Consistent with FMRP and Rac1 localization in dendritic fine structures, CYFIP1/2 are present in synaptosomal extracts.

A proposed program for national action to combat mental retardation ; report to the President.

Mode of access: Internet.

Assessment of behavior problems in persons with mental retardation living in the community : report on a workshop, September 9, 1988 /

Mode of access: Internet.

Mental retardation : plans for the future : public awareness, prevention, family and community service, systems simplification, full citizenship, international activities.

"15th annual report of the President's Committee on Mental Retardation."--T.P. verso.

Mental retardation : prevention strategies that work /

"Twelfth annual report"--Prelim. p.

Assessment of the national effort to combat mental retardation from biomedical causes : conference proceedings, November 14-16, 1983, Washington, D.C.

Item 529-B-8

Mental retardation : activities of the U.S. Department of Health, Education, and Welfare.

Description based on: 1962.

Compilation of selected public health laws : including particularly the Public Health Service Act, the Clean Air Act, the Solid Waste Disposal Act, the Mental Retardation Facilities and Community Mental Health Centers Construction Act, and the Federal Water Pollution Control Act.

Mode of access: Internet.

Compilation of selected public health laws: including particularly the Public health service act, the Clean air act, the Solid waste disposal act, the Mental retardation facilities and community mental health centers construction act, and the Narcotic addict rehabilitation act, the Federal food, drug, and cosmetic act, the Federal hazardous substances act, and the fair packaging and labeling act.

Prepared for the use of the Senate Committee on Labor and Public Welfare and the House Committee on Interstate and Foreign Commerce.

Self-esteem and job satisfaction of adults with mild mental retardation in sheltered workshops and supported employment programs

A sample of 200 adults with mild mental retardation were assessed on overall job satisfaction and self-esteem using the Vocational Program Evaluation Profile and the Coopersmith Self-esteem Inventory. The subjects worked either in a sheltered workshop or in a supported employment setting. Results indicated that there was a significant relationship between self-esteem and job satisfaction for both groups of subjects. In addition, subjects who worked in supported employment reported significantly higher levels of job satisfaction also. There was also an interaction between place of residence and place of employment when looking at self-esteem; those who live in a semi-independent home and work in supported employment reported the highest levels of self-esteem. These results are discussed in terms of the social validity of supported-employment for persons with mild mental retardation. ^

The effect of self-operated prompts on leisure participation by persons with mental retardation

The use of permanent prompts for individuals with severe disabilities has been shown to be effective in acquiring new skills, improving the accuracy and maintenance of existing skills, and in eliminating the need for trainer prompts. However, this technology has not been evaluated for its potential impact in promoting leisure participation. In this study, two men with mental retardation were administered auditory and/or visual prompts to investigate their effect on increasing participation in a leisure activity. In addition, their performance was evaluated to establish whether continuous versus intermittent schedules of the prompts would influence participation. The data were collected using a partial interval observation system and evaluated using a multiple baseline and an alternating treatment design. While both men increased their participation modestly in the leisure activity, there was no substantial difference between the two prompting schedules. ^