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http://dx.doi.org/10.1002/syn.21562 | DOI Listing |
bioRxiv
September 2024
University of Pittsburgh, Department of Cell Biology.
AAA+ proteins are essential molecular motors involved in numerous cellular processes, yet their mechanism of action in extracting membrane proteins from lipid bilayers remains poorly understood. One roadblock for mechanistic studies is the inability to generate subunit specific mutations within these hexameric proteins. Using the mitochondrial AAA+ protein Msp1 as a model, we created covalently linked dimers with varying combinations of wild type and catalytically inactive E193Q mutations.
View Article and Find Full Text PDFPoult Sci
August 2024
Animal Bioscience and Biotechnology Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, USA. Electronic address:
Interleukin-23 (IL-23) is a recently identified member of the IL-12 family of heterodimeric cytokines that play a critical role in regulating T helper cell function. IL-12 and IL-23 share a common p40 subunit, but differ in their p35 and p19 subunits, respectively. This difference in subunit composition results in distinct signaling pathways and biological functions for IL-12 and IL-23.
View Article and Find Full Text PDFMol Cell
April 2023
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Chemical Biology Program, Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, UA. Electronic address:
The mammalian SWI/SNF (mSWI/SNF or BAF) family of chromatin remodeling complexes play critical roles in regulating DNA accessibility and gene expression. The three final-form subcomplexes-cBAF, PBAF, and ncBAF-are distinct in biochemical componentry, chromatin targeting, and roles in disease; however, the contributions of their constituent subunits to gene expression remain incompletely defined. Here, we performed Perturb-seq-based CRISPR-Cas9 knockout screens targeting mSWI/SNF subunits individually and in select combinations, followed by single-cell RNA-seq and SHARE-seq.
View Article and Find Full Text PDFAutoantibodies against central nervous system proteins are increasingly being recognized in association with neurologic disorders. Although a growing number of neural autoantibodies have been identified, a causal link between specific autoantibodies and disease symptoms remains unclear, as most studies use patient-derived CSF-containing mixtures of autoantibodies. This raises questions concerning mechanism of action and which autoantibodies truly contribute to disease progression.
View Article and Find Full Text PDFInt J Neuropsychopharmacol
November 2022
RG Animal Models in Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute of Mental Health, Mannheim Faculty, Heidelberg University, Mannheim, Germany.
Rapastinel, formerly Glyx-13, is a novel positive allosteric modulator of the N-methyl-D-aspartate-receptor (NMDAR) that counteracts psychotomimetic actions of NMDAR antagonists. We set out to evaluate the effect of rapastinel alone or in combination with the global and GluN2B subunit-specific NMDAR antagonists MK-801 and Ro25-6981, respectively, on neuronal activation in relevant regions using c-fos brain mapping. Whereas rapastinel alone did not trigger significant c-fos expression beyond the prelimbic cortex, it strongly increased the c-fos expression induced by MK-801 in hippocampal, cingulate, and retrosplenial areas.
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