The nuclear compartment is delimited by a specialized expanded sheet of the endoplasmic reticulum (ER) known as the nuclear envelope (NE). Compared to the outer nuclear membrane and the contiguous peripheral ER, the inner nuclear membrane (INM) houses a unique set of transmembrane proteins that serve a staggering range of functions. Many of these functions reflect the exceptional position of INM proteins at the membrane-chromatin interface. Recent research revealed that numerous INM proteins perform crucial roles in chromatin organization, regulation of gene expression, genome stability, and mediation of signaling pathways into the nucleus. Other INM proteins establish mechanical links between chromatin and the cytoskeleton, help NE remodeling, or contribute to the surveillance of NE integrity and homeostasis. As INM proteins continue to gain prominence, we review these advancements and give an overview on the functional versatility of the INM proteome.
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http://dx.doi.org/10.1101/cshperspect.a040477 | DOI Listing |
Nat Commun
January 2025
Institute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre Juelich, Juelich, Germany.
Targeting of diseased cells is one of the most urgently needed prerequisites for a next generation of potent pharmaceuticals. Different approaches pursued fail mainly due to a lack of specific surface markers. Developing an RNA-based methodology, we can now ensure precise cell targeting combined with selective expression of effector proteins for therapy, diagnostics or cell steering.
View Article and Find Full Text PDFNat 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.
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