Fractionation of mouse hippocampus yields the postsynaptic proteome. 707 A) Total lysate and postsynaptic density (PSD) enriched fractions from mouse models of autism 708 spectrum disorder (ASD) demonstrate qualitative enrichment for the synaptic marker PSD95 by Western 709 blot (4 μg each sample). B) Comparative proteomics scheme showing parallel processing of 710 hippocampal synaptic fractions from ASD mouse models and their control samples. Shank3* and 711 Cacna1c* models were only assayed in Experiment 1, and both Anks1b Het samples were assayed in 712 Experiment 2. C) Gene ontology (GO) analysis of the postsynaptic proteome in STRING (Experiment 713 1) showed enrichment for cellular components and reactome pathways (D) expected for synaptic 714 fractions. 715
Impaired synaptic function is a common phenotype in animal models for autism spectrum disorder (ASD), and ASD risk genes are enriched for synaptic function. Here we leverage the availability of multiple ASD mouse models exhibiting synaptic deficits and behavioral correlates of ASD and use quantitative mass spectrometry with isobaric tandem mass tag...
Microexons are small sized (≤51 bp) exons which undergo extensive alternative splicing in neurons, microglia, embryonic stem cells, and cancer cells, giving rise to cell type specific protein isoforms. Due to their small sizes, microexons provide a unique challenge for the splicing machinery. They frequently lack exon splicer enhancers/repressors and require specialized neighboring trans-regulatory and cis-regulatory elements bound by RNA binding proteins (RBPs) for their inclusion. The functional consequences of including microexons within mRNAs have been extensively documented in the central nervous system (CNS) and aberrations in their inclusion have been observed to lead to abnormal processes. Despite the increasing evidence for microexons impacting cellular physiology within CNS, mechanistic details illustrating their functional importance in diseases of the CNS is still limited. In this review, we discuss the unique characteristics of microexons, and how RBPs participate in regulating their inclusion and exclusion during splicing. We consider recent findings of microexon alternative splicing and their implication for regulating the function of small GTPases in the context of the microglia, and we extrapolate these findings to what is known in neurons. We further discuss the emerging evidence for dysregulation of the Rho GTPase pathway in CNS diseases and the consequences contributed by the mis-splicing of microexons. This article is categorized under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing Regulation/Alternative Splicing RNA in Disease and Development > RNA in Disease.