Similar Datasets
Project description:Genes encoding subunits of the BAF (mammalian SWI/SNF) ATP-dependent chromatin remodeling complex are among the those most enriched for deleterious de novo mutations in intellectual disabilities and autism spectrum disorder, but the causative molecular pathways are not understood. Synaptic activity in neurons is critical for learning and memory and proper neural development. While BAF is required for activity-dependent developmental processes, such as dendritic outgrowth, the immediate molecular consequences of neuronal activity on BAF complexes are unknown. Here we report that neuronal activity induces dramatic remodeling of the subunit composition of BAF complexes within 15 minutes, concurrent with both phosphorylation and dephosphorylation of its subunits. These biochemical effects are a convergent phenomenon downstream of multiple calcium-activated signaling pathways in neurons and fibroblasts and correspond to changes in BAF-dependent chromatin accessibility. Our studies imply that BAF decodes signals at the membrane by altering the combinatorial composition of its subunits.
2025-03-15 | GSE245254 | GEO
Project description:Genes encoding subunits of the BAF (mammalian SWI/SNF) ATP-dependent chromatin remodeling complex are among the those most enriched for deleterious de novo mutations in intellectual disabilities and autism spectrum disorder, but the causative molecular pathways are not understood. Synaptic activity in neurons is critical for learning and memory and proper neural development. While BAF is required for activity-dependent developmental processes, such as dendritic outgrowth, the immediate molecular consequences of neuronal activity on BAF complexes are unknown. Here we report that neuronal activity induces dramatic remodeling of the subunit composition of BAF complexes within 15 minutes, concurrent with both phosphorylation and dephosphorylation of its subunits. These biochemical effects are a convergent phenomenon downstream of multiple calcium-activated signaling pathways in neurons and fibroblasts and correspond to changes in BAF-dependent chromatin accessibility. Our studies imply that BAF decodes signals at the membrane by altering the combinatorial composition of its subunits.
2025-03-15 | GSE245251 | GEO
Project description:Genes encoding subunits of the BAF (mammalian SWI/SNF) ATP-dependent chromatin remodeling complex are among the those most enriched for deleterious de novo mutations in intellectual disabilities and autism spectrum disorder, but the causative molecular pathways are not understood. Synaptic activity in neurons is critical for learning and memory and proper neural development. While BAF is required for activity-dependent developmental processes, such as dendritic outgrowth, the immediate molecular consequences of neuronal activity on BAF complexes are unknown. Here we report that neuronal activity induces dramatic remodeling of the subunit composition of BAF complexes within 15 minutes, concurrent with both phosphorylation and dephosphorylation of its subunits. These biochemical effects are a convergent phenomenon downstream of multiple calcium-activated signaling pathways in neurons and fibroblasts and correspond to changes in BAF-dependent chromatin accessibility. Our studies imply that BAF decodes signals at the membrane by altering the combinatorial composition of its subunits.
2025-03-15 | GSE292056 | GEO
Project description:Synaptic Activity Causes Minute-scale Changes in BAF Complex Composition and Function
| PRJNA1027458 | ENA
Project description:Synaptic Activity Causes Minute-scale Changes in BAF Complex Composition and Function [ATAC-Seq]
| PRJNA1027470 | ENA
Project description:Synaptic Activity Causes Minute-scale Changes in BAF Complex Composition and Function [RNA-Seq]
| PRJNA1027473 | ENA
Project description:Synaptic Activity Causes Minute-scale Changes in BAF Complex Composition and Function [CUT&Run]
| PRJNA1236400 | ENA
Project description:Cancer-associated, loss-of-function mutations in genes encoding subunits of the BRG1/BRM-associated factor (BAF) chromatin-remodeling complexes1-8 often cause drastic chromatin accessibility changes, especially in important regulatory regions9-19. However, it remains unknown how these changes are established over time (for example, immediate consequences or long-term adaptations), and whether they are causative for intracomplex synthetic lethalities, abrogating the formation or activity of BAF complexes9,20-24. In the present study, we use the dTAG system to induce acute degradation of BAF subunits and show that chromatin alterations are established faster than the duration of one cell cycle. Using a pharmacological inhibitor and a chemical degrader of the BAF complex ATPase subunits25,26, we show that maintaining genome accessibility requires constant ATP-dependent remodeling. Completely abolishing BAF complex function by acute degradation of a synthetic lethal subunit in a paralog-deficient background results in an almost complete loss of chromatin accessibility at BAF-controlled sites, especially also at superenhancers, providing a mechanism for intracomplex synthetic lethalities.
| S-EPMC7614082 | biostudies-literature
Project description:At the post-synaptic density (PSD), large protein complexes dynamically form and dissociate in response to synaptic activity, comprising the biophysical basis for learning and memory. The use of detergents to isolate the PSD and release its membrane-associated proteins complicates studies of these activity-dependent protein interaction networks, because detergents can simultaneously disrupt the very interactions under study. Despite widespread recognition that different detergents yield different experimental results, the effect of detergent on activity-dependent synaptic protein complexes has not been rigorously examined. Here, we characterize the effect of three detergents commonly used to study synaptic proteins on activity-dependent protein interactions. We first demonstrate that SynGAP-containing interactions are more abundant in 1% Deoxycholate (DOC), while Shank-, Homer- and mGluR5-containing interactions are more abundant in 1% NP-40 or Triton. All interactions were detected preferentially in high molecular weight complexes generated by size exclusion chromatography, although the detergent-specific abundance of proteins in high molecular weight fractions did not correlate with the abundance of detected interactions. Activity-dependent changes in protein complexes were consistent across detergent types, suggesting that detergents do not isolate distinct protein pools with unique behaviors. However, detection of activity-dependent changes is more or less feasible in different detergents due to baseline solubility. Collectively, our results demonstrate that detergents affect the solubility of individual proteins, but activity-dependent changes in protein interactions, when detectable, are consistent across detergent types.
| S-EPMC6659712 | biostudies-literature
Project description:Postsynaptic density protein 95 (PSD-95), a specialized scaffold protein with multiple protein interaction domains, forms the backbone of an extensive postsynaptic protein complex that organizes receptors and signal transduction molecules at the synaptic contact zone. Large, detergent-insoluble PSD-95-based postsynaptic complexes can be affinity-purified from conventional PSD fractions using magnetic beads coated with a PSD-95 antibody. In the present study purified PSD-95 complexes were analyzed by LC/MS/MS. A semiquantitative measure of the relative abundances of proteins in the purified PSD-95 complexes and the parent PSD fraction was estimated based on the cumulative ion current intensities of corresponding peptides. The affinity-purified preparation was largely depleted of presynaptic proteins, spectrin, intermediate filaments, and other contaminants prominent in the parent PSD fraction. We identified 525 of the proteins previously reported in parent PSD fractions, but only 288 of these were detected after affinity purification. We discuss 26 proteins that are major components in the PSD-95 complex based upon abundance ranking and affinity co-purification with PSD-95. This subset represents a minimal list of constituent proteins of the PSD-95 complex and includes, in addition to the specialized scaffolds and N-methyl-d-aspartate (NMDA) receptors, an abundance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, small G-protein regulators, cell adhesion molecules, and hypothetical proteins. The identification of two Arf regulators, BRAG1 and BRAG2b, as co-purifying components of the complex implies pivotal functions in spine plasticity such as the reorganization of the actin cytoskeleton and insertion and retrieval of proteins to and from the plasma membrane. Another co-purifying protein (Q8BZM2) with two sterile alpha motif domains may represent a novel structural core element of the PSD.
| S-EPMC2096750 | biostudies-literature