Several TCP genes have been reported to play important roles in plant development; the TCP homologs encode a plant-specific family of putative transcription factors. To understand the evolutionary relationship of TCP genes of Arabidopsis thaliana and Oryza sativa L. (hereafter called rice), we have identified 23 and 22 TCP genes in the Arabidopsis and rice genomes, respectively. Using phylogenetic analysis, we grouped these TCP genes into three classes. In addition, the motifs outside the TCP domain further support the evolutionary relationships among these genes. The genome distribution of the TCP genes strongly supports the hypothesis that genome-wide and tandem duplication contributed to the expansion of the TCP gene family. The expression pattern of the TCP genes was analyzed further, providing useful clues about the function of these genes.

Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder characterized by severe intellectual disability and other symptoms including autism. Although caused by the silencing of a single gene, Fmr1 (fragile X mental retardation 1), the complexity of FXS pathogenesis is amplified because the encoded protein, FMRP, regulates the activity-dependent translation of numerous mRNAs. Although the mRNAs that associate with FMRP have been extensively studied, little is known regarding the proteins whose expression levels are altered, directly or indirectly, by loss of FMRP during brain development. Here we systematically measured protein expression in neocortical synaptic fractions from Fmr1 knockout (KO) and wild-type (WT) mice at both adolescent and adult stages. Although hundreds of proteins are up-regulated in the absence of FMRP in young mice, this up-regulation is largely diminished in adulthood. Up-regulated proteins included previously unidentified as well as known targets involved in synapse formation and function and brain development and others linked to intellectual disability and autism. Comparison with putative FMRP target mRNAs and autism susceptibility genes revealed substantial overlap, consistent with the idea that the autism endophenotype of FXS is due to a "multiple hit" effect of FMRP loss, particularly within the PSD95 interactome. Through studies of de novo protein synthesis in primary cortical neurons from KO and WT mice, we found that neurons lacking FMRP produce nascent proteins at higher rates, many of which are synaptic proteins and encoded by FMRP target mRNAs. Our results provide a greatly expanded view of protein changes in FXS and identify age-dependent effects of FMRP in shaping the neuronal proteome.fragile X | quantitative mass spectrometry | synaptic protein synthesis | autism | stable isotope labeling F ragile X syndrome (FXS) is an X-linked monogenic disorder that leads to highly debilitating changes in neurodevelopment. Affected individuals exhibit mental retardation, attention deficit and hyperactivity, anxiety, autism spectrum behaviors, and other symptoms that compound overall impairment (1). In the vast majority of cases, FXS is caused by an mRNA-dependent epigenetic silencing of the Fmr1 (fragile X mental retardation 1) gene (2), which occurs secondarily to a CGG repeat expansion in the 5′ UTR region of Fmr1 (3) and results in absence of the encoded protein FMRP. FMRP is an RNA-binding protein that regulates several aspects of mRNA translation (1), transport (4), and stability (5) in neurons. Substantial evidence indicates that FMRP is particularly critical as a suppressor of activity-dependent mRNA translation at glutamatergic synapses (6, 7) and that loss of this function results in abnormalities in dendritic spine shape and several forms of long-term synaptic plasticity (8, 9). In addition, significant changes have been described regarding the structure and/or function of other synaptic systems, including GABAergic and endocannabinoid synapses (10, 11). Loss of FMR...

The spinal cord is extremely vulnerable to ischemia-reperfusion (I/R) injury, and the mitochondrion is the most crucial interventional target. Rapamycin can promote autophagy and exert neuroprotective effects in several diseases of the central nervous system. However, the impact of rapamycin via modulating mitophagy and apoptosis after spinal cord ischemia-reperfusion injury remains unclear. This study was undertaken to investigate the potential role of rapamycin in modulating mitophagy and mitochondria-dependent apoptosis using the spinal cord ischemia-reperfusion injury (SCIRI) mouse model. We found that rapamycin significantly (p < 0.05) enhanced mitophagy by increasing the translocation of p62 and Parkin to the damaged mitochondria in the mouse spinal cord injury model. At the same time, rapamycin significantly (p < 0.05) decreased mitochondrial apoptosis related protein (Apaf-1, Caspase-3, Caspase-9) expression by inhibiting Bax translocation to the mitochondria and the release of the cytochrome c from the mitochondria. After 24 h following SCIRI, rapamycin treatment reduced the TUNEL+ cells in the spinal cord ischemic tissue and improved the locomotor function in these mice. Our results therefore demonstrate that rapamycin can improve the locomotor function by promoting mitophagy and attenuating SCIRI -induced apoptosis, indicating its potential therapeutic application in a spinal cord injury.

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