The presynaptic active zone mediates synaptic vesicle exocytosis, and modulation of its molecular composition is important for many types of synaptic plasticity. Here, we identify synaptic scaffold protein liprin-α2 as a key organizer in this process. We show that liprin-α2 levels were regulated by synaptic activity and the ubiquitin-proteasome system. Furthermore, liprin-α2 organized presynapt...

Spatial and temporal regulation of intracellular Ca(2+) is a key event in many signaling pathways. Plasma membrane Ca(2+)-ATPases (PMCAs) are major regulators of Ca(2+) homeostasis and bind to PDZ (PSD-95/Dlg/ZO-1) domains via their C termini. Various membrane-associated guanylate kinase family members have been identified as interaction partners of PMCAs. In particular, SAP90/PSD95, PSD93/chap...

Channel changes customers W ith the right stimulation, an ion channel changes its stripes, say Man-Kyo Chung, Ali Guler, and Michael Caterina (Johns Hopkins School of Medicine, Baltimore, MD). Even ion channels that are a little promiscuous have their favorite passengers. Such channels were generally thought to stay true to their preferred customers. But Chung et al. found that the TRPV1 channe...

The neurofibromatosis type 1 (NF1) gene encodes a large tumor suppressor protein (neurofibromin). Although it is known to possess Ras GTPase-activating protein (GAP) activity, the cellular role of neurofibromin remains unclear. Here we used yeast two-hybrid screening to identify neurofibromin-interacting proteins. Syndecan-2, a transmembrane heparan sulfate proteoglycan (HSPG), was isolated as ...

PDZ (PSD-95/Disc large/Zonula occludens-1) protein interaction domains bind to cytoplasmic protein C-termini of transmembrane proteins. In order to identify new interaction partners of the voltage-gated L-type Ca channel Cav1.2 and the plasma membrane Ca ATPase 4b (PMCA4b), we used PDZ domain arrays probing for 124 PDZ domains.We confirmed this byGST pulldowns and immunoprecipitations. In PDZ a...

Alternative pre-mRNA splicing has a major impact on cellular functions and development with the potential to fine-tune cellular localization, posttranslational modification, interaction properties, and expression levels of cognate proteins. The plasticity of regulation sets the stage for cells to adjust the relative levels of spliced mRNA isoforms in response to stress or stimulation. As part o...

Dry casks for spent nuclear fuel (SNF) ensure the safe storage of SNF and provide radiation shielding. However, presence thick encompassing several layers steel concrete makes inspection a challenging task. Fast neutron interrogation is viable method nondestructive assay dry casks. In this study, we performed Monte Carlo simulation-based study associated with machine-learning-based image recons...