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JOURNAL ARTICLE
Wencai Qi, Yu Zhang, Mengting Li, Peipei Zhang, Jingjing Xing, Yanmei Chen, Liang Zhang
Endocytic recycling is an intracellular trafficking pathway that returns endocytosed molecules to the plasma membrane (PM) via the recycling endosome. This pathway plays a crucial role in remodeling PM composition and is thus essential for normal cellular homeostasis. In plants, endocytic recycling regulates the localization and abundance of receptors, transporters, and channels at the PM that are involved in many aspects of plant growth and development. Despite its importance, the recycling endosome and the underlying sorting mechanisms for cargo recycling in plants remain understudied in comparison to the endocytic recycling pathways of animal systems...
April 24, 2024: Journal of Experimental Botany
#2
REVIEW
Jennifer B Stott, Iain A Greenwood
The KCNQ family is comprised of five genes and the expression products form voltage-gated potassium channels (Kv7.1-7.5) that have a major impact upon cellular physiology in many cell types. Each functional Kv7 channel forms as a tetramer that often associates with proteins encoded by the KCNE gene family (KCNE1-5) and is critically reliant upon binding of phosphatidylinositol bisphosphate (PIP2 ) and calmodulin. Other modulators like A-kinase anchoring proteins, ubiquitin ligases and Ca-calmodulin kinase II alter Kv7 channel function and trafficking in an isoform specific manner...
2024: Frontiers in Physiology
#3
Matteo Gentili, Rebecca J Carlson, Bingxu Liu, Quentin Hellier, Jocelyn Andrews, Yue Qin, Paul C Blainey, Nir Hacohen
STING is an innate immune sensor that traffics across many cellular compartments to carry out its function of detecting cyclic di-nucleotides and triggering defense processes. Mutations in factors that regulate this process are often linked to STING-dependent human inflammatory disorders. To systematically identify factors involved in STING trafficking, we performed a genome-wide optical pooled screen and examined the impact of genetic perturbations on intracellular STING localization. Based on subcellular imaging of STING protein and trafficking markers in 45 million cells perturbed with sgRNAs, we defined 464 clusters of gene perturbations with similar cellular phenotypes...
April 9, 2024: bioRxiv
#4
REVIEW
Jinxuan Wang, Jianxiong Xu, Tianhu Liu, Chaoping Yu, Fengcheng Xu, Guixue Wang, Shun Li, Xiaozhen Dai
Biomechanical forces, including vascular shear stress, cyclic stretching, and extracellular matrix stiffness, which influence mechanosensitive channels in the plasma membrane, determine cell function in atherosclerosis. Being highly associated with the formation of atherosclerotic plaques, endocytosis is the key point in molecule and macromolecule trafficking, which plays an important role in lipid transportation. The process of endocytosis relies on the mobility and tension of the plasma membrane, which is sensitive to biomechanical forces...
2024: Frontiers in Cardiovascular Medicine
#5
JOURNAL ARTICLE
Hiroto Kohashi, Ryu Nagata, Yusuke Tamenori, Tomorrow Amatani, Yoshifumi Ueda, Yasuo Mori, Yuuya Kasahara, Satoshi Obika, Masahito Shimojo
Antisense oligonucleotide (ASO) therapy is a novel therapeutic approach in which ASO specifically binds target mRNA, resulting in mRNA degradation; however, cellular uptake of ASOs remains critically low, warranting improvement. Transient receptor potential canonical (TRPC) channels regulate Ca2+ influx and are activated upon stimulation by phospholipase C-generated diacylglycerol. Herein, we report that a novel TRPC3/C6/C7 activator, L687, can induce cellular ASO uptake. L687-induced ASO uptake was enhanced in a dose- and incubation-time-dependent manner...
April 16, 2024: Nucleic Acids Research
#6
JOURNAL ARTICLE
Dazhi Li, Cristian Rocha-Roa, Matthew A Schilling, Karin M Reinisch, Stefano Vanni
Glycerophospholipids are synthesized primarily in the cytosolic leaflet of the endoplasmic reticulum (ER) membrane and must be equilibrated between bilayer leaflets to allow the ER and membranes derived from it to grow. Lipid equilibration is facilitated by integral membrane proteins called "scramblases." These proteins feature a hydrophilic groove allowing the polar heads of lipids to traverse the hydrophobic membrane interior, similar to a credit card moving through a reader. Nevertheless, despite their fundamental role in membrane expansion and dynamics, the identity of most scramblases has remained elusive...
April 23, 2024: Proceedings of the National Academy of Sciences of the United States of America
#7
JOURNAL ARTICLE
Preksha Gaur, Yesheswini Rajendran, Bhagyashree Srivastava, Manasvini Markandey, Vered Fishbain-Yoskovitz, Gayatree Mohapatra, Aamir Suhail, Shikha Chaudhary, Shaifali Tyagi, Subhash Chandra Yadav, Amit Kumar Pandey, Yifat Merbl, Avinash Bajaj, Vineet Ahuja, Chittur Srikanth
Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier, coupled with microbial dysbiosis, has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis. In vivo Rab7 knocked down mice (Rab7KD ) displayed a compromised mucus layer, increased microbial permeability, and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis...
April 9, 2024: ELife
#8
JOURNAL ARTICLE
Xinxin Jing, Pengyue Wang, Jianjian Liu, Meirong Xiang, Xia Song, Chaonan Wang, Pengbai Li, Honglian Li, Zujian Wu, Chao Zhang
Potassium (K+ ) plays a crucial role as a macronutrient in the growth and development of plants. Studies have definitely determined the vital roles of K+ in response to pathogen invasion. Our previous investigations revealed that rice plants infected with rice grassy stunt virus (RGSV) displayed a reduction in K+ content, but the mechanism by which RGSV infection subverts K+ uptake remains unknown. In this study, we found that overexpression of RGSV P1, a specific viral protein encoded by viral RNA1, results in enhanced sensitivity to low K+ stress and exhibits a significantly lower rate of K+ influx compared to wild-type rice plants...
April 5, 2024: Plant Biotechnology Journal
#9
JOURNAL ARTICLE
Yutong Song, Zhihao Zhao, Linyu Xu, Peiyuan Huang, Jiayang Gao, Jingxuan Li, Xuejie Wang, Yiren Zhou, Jinhui Wang, Wenting Zhao, Likun Wang, Chaogu Zheng, Bo Gao, Liwen Jiang, Kai Liu, Yusong Guo, Xiaoqiang Yao, Liting Duan
The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner...
April 1, 2024: Developmental Cell
#10
Clara Houdayer, A Marie Phillips, Marie Chabbert, Jennifer Bourreau, Reza Maroofian, Henry Houlden, Kay Richards, Nebal Waill Saadi, Eliška Dad'ová, Patrick Van Bogaert, Mailys Rupin, Boris Keren, Perrine Charles, Thomas Smol, Audrey Riquet, Lynn Pais, Anne O'Donnell-Luria, Grace E VanNoy, Allan Bayat, Rikke S Møller, Kern Olofsson, Rami Abou Jamra, Steffen Syrbe, Majed Dasouki, Laurie H Seaver, Jennifer A Sullivan, Vandana Shashi, Fowzan S Alkuraya, Alexis F Poss, J Edward Spence, Rhonda E Schnur, Ian C Forster, Chaseley E Mckenzie, Cas Simons, Min Wang, Penny Snell, Kavitha Kothur, Michael Buckley, Tony Roscioli, Noha Elserafy, Benjamin Dauriat, Vincent Procaccio, Daniel Henrion, Guy Lenaers, Estelle Colin, Nienke E Verbeek, Koen L Van Gassen, Claire Legendre, Dominique Bonneau, Christopher A Reid, Katherine B Howell, Alban Ziegler, Christian Legros
Hyperpolarization activated Cyclic Nucleotide (HCN) gated channels are crucial for various neurophysiological functions, including learning and sensory functions, and their dysfunction are responsible for brain disorders, such as epilepsy. To date, HCN2 variants have only been associated with mild epilepsy and recently, one monoallelic missense variant has been linked to developmental and epileptic encephalopathy. Here, we expand the phenotypic spectrum of HCN2- related disorders by describing twenty-one additional individuals from fifteen unrelated families carrying HCN2 variants...
March 22, 2024: medRxiv
#11
JOURNAL ARTICLE
Chidinma Adanna Okolo, Jack Jonathan Maran, Amy Watts, Jaime Maripillan, Maria Harkiolaki, Agustín D Martínez, Colin R Green, Odunayo Omolola Mugisho
Non-junctional connexin43 (Cx43) plasma membrane hemichannels have been implicated in several inflammatory diseases, particularly playing a role in ATP release that triggers activation of the inflammasome. Therapies targeting the blocking of the hemichannels to prevent the pathological release or uptake of ions and signalling molecules through its pores are of therapeutic interest. To date, there is no close-to-native, high-definition documentation of the impact of Cx43 hemichannel-mediated inflammation on cellular ultrastructure, neither is there a robust account of the ultrastructural changes that occur following treatment with selective Cx43 hemichannel blockers such as Xentry-Gap19 (XG19)...
April 15, 2024: Heliyon
#12
JOURNAL ARTICLE
Jun Yang, Zhuonan Pu, Xiaorong Tao, Jiajia Liu, Ke Li, Jiawei Shi, Hui Qiao, Xing Fan
BACKGROUND: The KCa3.1 channel (KCNN4) is extensively investigated as an oncogene in human cancers. The current study aimed to explore the clinicopathological significance of KCNN4 expression in patients with primary adult-type diffuse gliomas. METHODS: Demographic, RNA-seq, and follow-up data of 477 patients were retrospectively reviewed. Patients were divided into the experimental and validation groups (278 and 199). KCNN4-related genes were determined by Pearson correlation analysis, and enrichment analyses and tumor-infiltrating immune cell assessments were applied to explore the potential mechanisms of KCNN4 involving glioma progression...
March 30, 2024: Translational Oncology
#13
JOURNAL ARTICLE
Mathieu Pizzonero, Rhalid Akkari, Xavier Bock, Romain Gosmini, Elsa De Lemos, Béranger Duthion, Gregory Newsome, Thi-Thu-Trang Mai, Virginie Roques, Hélène Jary, Jean-Michel Lefrancois, Laetitia Cherel, Vanessa Quenehen, Marielle Babel, Nuria Merayo, Natacha Bienvenu, Oscar Mammoliti, Ghjuvanni Coti, Adeline Palisse, Marlon Cowart, Anurupa Shrestha, Stephen Greszler, Steven Van Der Plas, Koen Jansen, Pieter Claes, Mia Jans, Maarten Gees, Monica Borgonovi, Gert De Wilde, Katja Conrath
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) protein. This epithelial anion channel regulates the active transport of chloride and bicarbonate ions across membranes. Mutations result in reduced surface expression of CFTR channels with impaired functionality. Correctors are small molecules that support the trafficking of CFTR to increase its membrane expression. Such correctors can have different mechanisms of action. Combinations may result in a further improved therapeutic benefit...
March 25, 2024: Journal of Medicinal Chemistry
#14
JOURNAL ARTICLE
Mingyue Li, Chunli Zhang, Yuntao Xu, Shaobai Li, Chenhui Huang, Jian Wu, Ming Lei
The endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved, multi-subunit complex acting as an insertase at the ER membrane. Growing evidence shows that the EMC is also involved in stabilizing and trafficking membrane proteins. However, the structural basis and regulation of its multifunctionality remain elusive. Here, we report cryo-electron microscopy structures of human EMC in apo- and voltage-dependent anion channel (VDAC)-bound states at resolutions of 3.47 Å and 3.32 Å, respectively...
March 15, 2024: Aging
#15
JOURNAL ARTICLE
Sarah C Simmons, William J Flerlage, Ludovic D Langlois, Ryan D Shepard, Christopher Bouslog, Emily H Thomas, Kaitlyn M Gouty, Jennifer L Sanderson, Shawn Gouty, Brian M Cox, Mark L Dell'Acqua, Fereshteh S Nugent
The scaffolding A-kinase anchoring protein 150 (AKAP150) is critically involved in kinase and phosphatase regulation of synaptic transmission/plasticity, and neuronal excitability. Emerging evidence also suggests that AKAP150 signaling may play a key role in brain's processing of rewarding/aversive experiences, however its role in the lateral habenula (LHb, as an important brain reward circuitry) is completely unknown. Using whole cell patch clamp recordings in LHb of male wildtype and ΔPKA knockin mice (with deficiency in AKAP-anchoring of PKA), here we show that the genetic disruption of PKA anchoring to AKAP150 significantly reduces AMPA receptor-mediated glutamatergic transmission and prevents the induction of presynaptic endocannabinoid-mediated long-term depression in LHb neurons...
March 20, 2024: Communications Biology
#16
REVIEW
Carlos M Farinha, Lúcia Santos, João F Ferreira
Trafficking of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is a complex process that starts with its biosynthesis and folding in the endoplasmic reticulum. Exit from the endoplasmic reticulum (ER) is coupled with the acquisition of a compact structure that can be processed and traffic through the secretory pathway. Once reaching its final destination-the plasma membrane, CFTR stability is regulated through interaction with multiple protein partners that are involved in its post-translation modification, connecting the channel to several signaling pathways...
2024: Frontiers in Cell and Developmental Biology
#17
JOURNAL ARTICLE
Sarah Charital, Serena Shunmugam, Sheena Dass, Anna Maria Alazzi, Christophe-Sébastien Arnold, Nicholas J Katris, Samuel Duley, Nyamekye A Quansah, Fabien Pierrel, Jérôme Govin, Yoshiki Yamaryo-Botté, Cyrille Y Botté
Apicomplexa parasites cause major diseases such as toxoplasmosis and malaria that have major health and economic burdens. These unicellular pathogens are obligate intracellular parasites that heavily depend on lipid metabolism for the survival within their hosts. Their lipid synthesis relies on an essential combination of fatty acids (FAs) obtained from both de novo synthesis and scavenging from the host. The constant flux of scavenged FA needs to be channeled toward parasite lipid storage, and these FA storages are timely mobilized during parasite division...
March 19, 2024: MBio
#18
JOURNAL ARTICLE
Mei-Yao Wu, An-Sheng Lee, Yen-Nien Lin, Wei-Hsin Chung, Ke-Wei Chen, Chiung-Ray Lu, Yun-Fang Chen, Chia-Ming Chang, Wei-Chung Tsai, Yi-Tzone Shiao, Chu-Huang Chen, Kuan-Cheng Chang
BACKGROUND: Early ventricular tachycardia/fibrillation (VT/VF) in patients with ST-elevation myocardial infarction (STEMI) has higher morbidity and mortality. This study examines gender-differentiated risk factors and underlying mechanisms for early onset VT/VF in STEMI. METHODS: We analyzed data from 2,964 consecutive STEMI patients between January 1, 2008 and December 31, 2021. Early VT/VF was defined as occurrence of spontaneous VT/VF of ≥30 s or requirement of immediate cardioversion/defibrillation within the first 48 h after symptoms...
2024: Frontiers in Cardiovascular Medicine
#19
JOURNAL ARTICLE
Francisco M Cruz, Álvaro Macías, Ana I Moreno-Manuel, Lilian K Gutiérrez, María Linarejos Vera-Pedrosa, Isabel Martínez-Carrascoso, Patricia Sánchez Pérez, Juan Manuel Ruiz Robles, Francisco J Bermúdez-Jiménez, Aitor Díaz-Agustín, Fernando Martínez de Benito, Salvador Arias-Santiago, Aitana Braza-Boils, Mercedes Martín-Martínez, Marta Gutierrez-Rodríguez, Juan A Bernal, Esther Zorio, Juan Jiménez-Jaimez, José Jalife
BACKGROUND: Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122 -to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122 -to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2...
March 18, 2024: Circulation Research
#20
Shekinah Phillips, John Chatham, Lori L McMahon
GABAergic transmission is influenced by post-translational modifications, like phosphorylation, impacting channel conductance, allosteric modulator sensitivity, and membrane trafficking. O-GlcNAcylation is a post-translational modification involving the O-linked attachment of β-N-acetylglucosamine on serine/threonine residues. Previously we reported an acute increase in O-GlcNAcylation elicits a long-term depression of evoked GABA A R inhibitory post synaptic currents (eIPSCs) onto hippocampal principal cells...
March 6, 2024: bioRxiv
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