T-Cell activation: a queuing theory analysis at low agonist density [PDF]
We analyze a simple linear triggering model of the T-cell receptor (TCR) within the framework of queuing theory, in which TCRs enter the queue upon full activation and exit by downregulation.
Bossi+61 more
core +2 more sources
Ion channel function of polycystin‐2/polycystin‐1 heteromer revealed by structure‐guided mutagenesis
Mutations in polycystin‐1 (PC1) or polycystin‐2 (PC2) cause autosomal‐dominant polycystic kidney disease (ADPKD). We generated a novel gain‐of‐function PC2/PC1 heteromeric ion channel by mutating pore‐blocking residues. Moreover, we demonstrated that PC2 will preferentially assemble with PC1 to form heteromeric complexes when PC1 is co‐expressed ...
Tobias Staudner+7 more
wiley +1 more source
CINs of the cytoplasm: dissecting dsRNA signaling in chromosomal instability
Micronuclei, formed during cell division in chromosomal instability settings, rupture and lead to the accumulation of immunogenic double‐stranded RNA in the cytoplasm, activating MAVS‐dependent interferon signaling and innate antitumor immunity.
Aglaia Skolariki+2 more
wiley +1 more source
A Gq Biased Small Molecule Active at the TSH Receptor
G protein coupled receptors (GPCRs) can lead to G protein and non-G protein initiated signals. By virtue of its structural property, the TSH receptor (TSHR) has a unique ability to engage different G proteins making it highly amenable to selective ...
Rauf Latif+9 more
doaj +1 more source
TRPM8 levels determine tumor vulnerability to channel agonists
TRPM8 is a Ca2+ permissive channel. Regardless of the amount of its transcript, high levels of TRPM8 protein mark different tumors, including prostate, breast, colorectal, and lung carcinomas. Targeting TRPM8 with channel agonists stimulates inward calcium currents followed by emptying of cytosolic Ca2+ stores in cancer cells.
Alessandro Alaimo+18 more
wiley +1 more source
Ligand-dependent opening of the multiple AMPA receptor conductance states: a concerted model [PDF]
Modulation of the properties of AMPA receptors at the post-synaptic membrane is one of the main suggested mechanisms behind synaptic plasticity in the central nervous system of vertebrates. Electrophysiological recordings of single channels stimulated with agonists showed that both recombinant and native AMPA receptors visit multiple conductance states
arxiv +1 more source
In vitro and in vivo pharmacological activities of 14-o-phenylpropyloxymorphone, a potent mixed mu/delta/kappa-opioid receptor agonist with reduced constipation in mice [PDF]
Pain, particularly chronic pain, is still an unsolved medical condition. Central goals in pain control are to provide analgesia of adequate efficacy and to reduce complications associated with the currently available drugs.
Lattanzi, Roberta+4 more
core +2 more sources
Understanding and measuring mechanical signals in the tumor stroma
This review discusses cancer‐associated fibroblast subtypes and their functions, particularly in relation to extracellular matrix production, as well as the development of 3D models to study tumor stroma mechanics in vitro. Several quantitative techniques to measure tissue mechanical properties are also described, to emphasize the diagnostic and ...
Fàtima de la Jara Ortiz+3 more
wiley +1 more source
T2DM is characterized by peripheral blood insulin resistance and progressive pancreatic β‐cell dysfunction. Here, we showed that AQP7, the only aquaglyceroporin protein, regulates autophagy and apoptosis in pancreatic β‐cells. We propose the existence of a positive feedback loop between MAPK signaling and AQP7 that regulates autophagy and apoptosis in ...
Maoqi Wang+5 more
wiley +1 more source
Cyclic nucleotide-gated channels: structural basis of ligand efficacy and allosteric modulation [PDF]
Most working proteins, including metabolic enzymes, transcription regulators, and membrane receptors, transporters, and ion channels, share the property of allosteric coupling. The term 'allosteric' means that these proteins mediate indirect interactions
Lester, Henry A.+2 more
core +1 more source