Slitrk5 Mediates BDNF-Dependent TrkB Receptor Trafficking and Signaling.

Recent studies in humans and in genetic mouse models have identified Slit- and NTRK-like family (Slitrks) as candidate genes for neuropsychiatric disorders. All Slitrk isotypes are highly expressed in the CNS, where they mediate neurite outgrowth, synaptogenesis, and neuronal survival. However, the molecular mechanisms underlying these functions are not known.

A role for dendritic mGluR5-mediated local translation of Arc/Arg3.1 in MEF2-dependent synapse elimination.

Experience refines synaptic connectivity through neural activity-dependent regulation of transcription factors. Although activity-dependent regulation of transcription factors has been well described, it is unknown whether synaptic activity and local, dendritic regulation of the induced transcripts are necessary for mammalian synaptic plasticity in response to transcription factor activation. Neuronal depolarization activates the myocyte enhancer factor 2 (MEF2) family of transcription factors that suppresses excitatory synapse number.

Genes, brain, and behavior: development gone awry in autism? A report on the 23rd Annual International Symposium of the Center for the Study of Gene Structure and Function.

Autism and its highly variable symptomology were the themes of the 23rd Annual International Symposium of the Center for the Study of Gene Structure and Function at Hunter College in New York City, held 15 January 2010. The meeting explored the extensive research on autism from several perspectives-integrating research on genetics, neuroscience, and behavior-from researchers presenting new and innovative approaches to understanding the autism spectrum. Early diagnosis, intervention, and genetics were major themes because they are seen as essential areas in which progress is needed before the rise in numbers of cases of autism throughout the world, which some describe as approaching an epidemic, can be stemmed.

A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome.

The function of local protein synthesis in synaptic plasticity and its dysregulation in fragile X syndrome (FXS) is well studied, however the contribution of regulated mRNA transport to this function remains unclear. We report a function for the fragile X mental retardation protein (FMRP) in the rapid, activity-regulated transport of mRNAs important for synaptogenesis and plasticity. mRNAs were deficient in glutamatergic signaling-induced dendritic localization in neurons from Fmr1 KO mice, and single mRNA particle dynamics in live neurons revealed diminished kinesis.

Dynamic association of the fragile X mental retardation protein as a messenger ribonucleoprotein between microtubules and polyribosomes.

The fragile X mental retardation protein (FMRP) is a selective RNA-binding protein that regulates translation and plays essential roles in synaptic function. FMRP is bound to specific mRNA ligands, actively transported into neuronal processes in a microtubule-dependent manner, and associated with polyribosomes engaged in translation elongation. However, the biochemical relationship between FMRP-microtubule association and FMRP-polyribosome association remains elusive.

Imaging mRNA movement from transcription sites to translation sites.

RNA localization is one mechanism to temporally and spatially restrict protein synthesis to specific subcellular compartments in response to extracellular stimuli. To understand the mechanisms of mRNA localization, a number of methods have been developed to follow the path of these molecules in living cells including direct labeling of target mRNAs, the MS2-GFP system, and molecular beacons. We review advances in these methods with the goal of identifying the particular strengths and weaknesses of the various approaches in their ability to follow the movements of mRNAs from transcription sites to translation sites.

Metabotropic glutamate receptor activation regulates fragile x mental retardation protein and FMR1 mRNA localization differentially in dendrites and at synapses.

Fragile X syndrome is caused by the absence of the mRNA-binding protein Fragile X mental retardation protein (FMRP), which may play a role in activity-regulated localization and translation of mRNA in dendrites and at synapses. We investigated whether neuronal activity and glutamatergic signals regulate trafficking of FMRP and its encoding Fmr1 mRNA into dendrites or at synapses. Using high-resolution fluorescence and digital imaging microscopy in cultured hippocampal neurons, FMRP and Fmr1 mRNA were localized in granules throughout dendrites and within spines.

Hyperlipidemic effects of trans fatty acids are accentuated by dietary cholesterol in gerbils.

Trans isomers of dietary fatty acids, generated during the commercial hydrogenation of unsaturated fats, may contribute to coronary heart disease (CHD) in humans by interfering with lipid metabolism. To examine this possibility in a fat-sensitive model, the Mongolian gerbil (Meriones unguiculatus) was used to compare the cholesterolemic and triglyceridemic potential of modest increments of trans fatty acids from partially hydrogenated soybean oil with other saturated fatty acids in the presence and absence of dietary cholesterol. Age-, dose-, and time-dependent effects were examined in weanling, 6-month-old, and 1-year-old gerbils.