PSD95-DLG-ZO1 domain-containing proteins of the ProSAP/Shank family are major scaffolding proteins of the neuronal postsynaptic density which play a pivotal role in the linkage of membrane receptors to downstream signal effectors and the actin-based cytoskeleton. Recently, ProSAP1/Shank2 has also been localized in various non-neuronal cells where it may fulfill similar functions as in neurons. We now complement these data by the study of ProSAP/Shank expression at the mRNA and protein level in a primary lymphoid organ, i.e., the thymus. Transcripts for ProSAP1/Shank2, the spliceoform Shank2E, and ProSAP2/Shank3 could be clearly detected in the thymus. Western blot and immunocytochemical analyses verified the presence of ProSAP1/Shank2 and ProSAP2/Shank3 proteins in thymic tissue. Immunoreactivity was concentrated in the whole peripheral cytoplasm of thymocytes underneath the plasma membrane. Discrete subplasmalemmal areas of pronounced ProSAP/Shank immunoreactivity could be demonstrated inside several thymocytes by confocal laser scanning microscopy. Our results establish ProSAP/Shank as a constituent of the cell cortex of thymocytes and thus lead to the hypothesis that ProSAP/Shank proteins serve as a platform for the coordination of membrane receptor-dependent signal transduction in immune cells.
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http://dx.doi.org/10.1007/s00418-006-0199-9 | DOI Listing |
In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory, inhibitory, and medium spiny neurons and the involvement of amygdala neurons in both mouse and human single-cell analyses.
View Article and Find Full Text PDFChin Med J (Engl)
January 2025
Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
Background: Neurological dysfunction is a common complication of traumatic brain injury (TBI), and early treatments are critical for the long-term prognosis. This study aimed to investigate whether hypidone hydrochloride (YL-0919) improves neurological function impairment in mice with TBI.
Methods: TBI was induced in adult male C57BL/6J mice using the controlled cortical impact (CCI) method.
Int J Mol Sci
December 2024
Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
Induced pluripotent stem cell (iPSC)-derived neurons (iNs) have been widely used as models of neurodevelopment and neurodegenerative diseases. Coating cell culture vessels with extracellular matrixes (ECMs) gives structural support and facilitates cell communication and differentiation, ultimately enhances neuronal functions. However, the relevance of different ECMs to the natural environment and their impact on neuronal differentiation have not been fully characterized.
View Article and Find Full Text PDFNeurobiol Dis
January 2025
Department of Anesthesiology, Hebei Province, Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China,. Electronic address:
Background: Reports indicate that depression is a common mental health issue following traumatic brain injury (TBI). Our prior research suggests that Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-related neuroinflammation, modulated by glial cells such as astrocytes, is likely to play a crucial role in the progression of anxiety and cognitive dysfunction. However, there is limited understanding of the potential of astrocytic NLRP3 in treating depression under mild TBI condition.
View Article and Find Full Text PDFAlzheimers Dement
January 2025
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Introduction: Plaques are a hallmark feature of Alzheimer's disease (AD). We found that the loss of mucosal-associated invariant T (MAIT) cells and their antigen-presenting molecule MR1 caused a delay in plaque pathology development in AD mouse models. However, it remains unknown how this axis is impacting dystrophic neurites.
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