The inner nuclear membrane (INM) of eukaryotic cells is enriched in proteins that are required for nuclear structure, chromosome organization, DNA repair, and transcriptional control. Mislocalization of INM proteins is observed in a wide spectrum of human diseases; however, the mechanism by which INM proteins reach their final destination is poorly understood. In this review we discuss how investigating INM composition, dissecting targeting pathways of conserved INM proteins in multiple systems and analyzing the nuclear transport of viruses and signaling complexes have broadened our knowledge of INM transport to include both nuclear pore complex-dependent and -independent pathways. The study of these INM targeting pathways is important to understanding nuclear organization and in both normal and diseased cells.
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http://dx.doi.org/10.1016/j.tcb.2013.10.006 | DOI Listing |
Nat Rev Drug Discov
January 2025
Euler Institute, Faculty of Biomedical Sciences, Università della Svizzera italiana (USI), Lugano, Switzerland.
G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at their orthosteric binding site. Despite their prominence, predicting the pharmacological effects of novel GPCR-targeting drugs remains challenging due to the complex functional dynamics of these receptors.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
National Measurement Laboratory, LGC, Queens Road, TW11 0LY Teddington, U.K.
Neurofilament light chain (NfL) is an early nonspecific biomarker in neurodegenerative diseases and traumatic brain injury, indicating axonal damage. This work describes the detailed structural characterization of a selected primary calibrator with the potential to be used in future reference measurement procedure (RMP) development for the accurate quantification of NfL. As a part of the described workflow, the sequence, higher-order structure as well as solvent accessibility, and hydrogen-bonding profile were assessed under three different conditions in KPBS, artificial cerebrospinal fluid, and artificial cerebrospinal fluid in the presence of human serum albumin.
View Article and Find Full Text PDFAlzheimers Res Ther
December 2024
Department of Neurology, Ulm University Hospital, 89081, Ulm, Germany.
Introduction: The differentiation between Alzheimer's disease (AD) and behavioral-variant frontotemporal dementia (bvFTD) can be complicated in the initial phase by shared symptoms and pathophysiological traits. Nevertheless, advancements in understanding AD's diverse pathobiology suggest the potential for establishing blood-based methods for differential diagnosis.
Methods: We devised a novel assay combining immunoprecipitation and mass spectrometry (IP-MS) to quantify Amyloid-beta (Aβ) peptides in plasma.
Methods Mol Biol
December 2024
INM-Leibniz Institute for New Materials, Saarbrücken, Germany.
Methods for the precise temporal control of cell surface receptor activation are indispensable for the investigation of signaling processes in mammalian cells. Optogenetics enables such precise control, but its application in primary cells is limited by the imperative for genetic manipulation of target cells. We here describe a method that overcomes this obstacle and enables the precise activation of the T cell receptor in nongenetically engineered human T cells by light.
View Article and Find Full Text PDFBiochem Biophys Res Commun
January 2025
Section of Host Defences, Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama-shi, Toyama, 930-0194, Japan. Electronic address:
Asialo-GM1 (ASGM1) has been identified as a cell surface marker of murine NK cells. Although polyclonal anti-asialo-GM1 antibodies (anti-ASGM1 pAb) have been widely used for studying natural killer (NK) cell functions in vivo, the technical challenges have existed in their specificity for NK cell depletion. Furthermore, the exact expression of ASGM1 on the NK cell lineage and other immune cells has not been characterized due to the lack of appropriate reagents.
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