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JOURNAL ARTICLE
Yan Xu, Wenxin Li, Ya Chen, Tianjun Xu, Yuena Sun
Signal transducing adapter molecule 2 (STAM2), a member of the Signal Transducing Adapter Molecule (STAM) family, is a protein with significant implications in diverse signaling pathways and endocytic membrane trafficking. However, the role of the STAM2 especially in fish, remains largely unknown. In this study, we discover that STAM2 negatively regulates the NF-κB signaling pathway, and its inhibitory effect is enhanced upon LPS induction. Our study confirms that STAM2 can enhance the degradation of Adaptor molecule myeloid differentiation primary-response protein 88 (MyD88), an upstream regulator of NF-κB pathway activation...
April 7, 2024: Fish & Shellfish Immunology
#22
JOURNAL ARTICLE
Amanda J Macke, Taylor E Divita, Artem N Pachikov, Sundararajan Mahalingam, Ramesh Bellamkonda, Karuna Rasineni, Carol A Casey, Armen Petrosyan
The development of alcohol-associated liver disease (ALD) is associated with disorganized Golgi apparatus and accelerated phagophore formation. While Golgi membranes may contribute to phagophores, association between Golgi alterations and macroautophagy/autophagy remains unclear. GOLGA4/p230 (golgin A4), a dimeric Golgi matrix protein, participates in phagophore formation, but the underlying mechanism is elusive. Our prior research identified ethanol (EtOH)-induced Golgi scattering, disrupting intra-Golgi trafficking and depleting RAB3D GTPase from the trans -Golgi...
April 9, 2024: Autophagy
#23
REVIEW
O Adeoye Akinwunmi
Most chemicals expressed in mammalian cells have complex delivery and transport mechanisms to get to the right intracellular sites. One of these mechanisms transports most transmembrane proteins, as well as almost all secreted proteins, from the endoplasmic reticulum, where they are formed, to their final location. Nearly all eukaryotic cells have a membrane trafficking mechanism that is both a prominent and critical component. This system, which consists of dynamically coupled compartments, supports the export and uptake of extracellular material, remodeling and signaling at the cellular interface, intracellular alignment, and maintenance of internal compartmentalization (organelles)...
October 2023: Archives of Razi Institute
#24
JOURNAL ARTICLE
Hayate Watanabe, Shingo Urano, Nozomi Kikuchi, Yurika Kubo, Ayumi Kikuchi, Katsuya Gomi, Takahiro Shintani
The soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex forms a 4-helix coiled-coil bundle consisting of 16 layers of interacting side chains upon membrane fusion. The central layer (layer 0) is highly conserved and comprises three glutamines (Q) and one arginine (R), and thus SNAREs are classified into Qa-, Qb-, Qc-, and R-SNAREs. Homotypic vacuolar fusion in Saccharomyces cerevisiae requires the SNAREs Vam3 (Qa), Vti1 (Qb), Vam7 (Qc), and Nyv1 (R). However, the yeast strain lacking NYV1 (nyv1Δ) shows no vacuole fragmentation, whereas the vam3Δ and vam7Δ strains display fragmented vacuoles...
April 6, 2024: Journal of Biological Chemistry
#25
JOURNAL ARTICLE
Arthur Beauchet, Norbert Bollier, Magali Grison, Valérie Rofidal, Frédéric Gévaudant, Emmanuelle Bayer, Nathalie Gonzalez, Christian Chevalier
FW2.2 (standing for FRUIT WEIGHT 2.2), the founding member of the CELL NUMBER REGULATOR (CNR) gene family, was the first cloned gene underlying a quantitative trait locus (QTL) governing fruit size and weight in tomato (Solanum lycopersicum). However, despite this discovery over 20 years ago, the molecular mechanisms by which FW2.2 negatively regulates cell division during fruit growth remain undeciphered. In the present study, we confirmed that FW2.2 is a membrane-anchored protein whose N- and C-terminal ends face the apoplast...
April 8, 2024: Plant Physiology
#26
JOURNAL ARTICLE
Keiko Gengyo-Ando, Masahiko Kumagai, Hideki Ando, Junichi Nakai
The Sec1/Munc18 (SM) protein VPS45 is a key regulator of SNARE-mediated membrane fusion in endosomal trafficking, but its precise role remains unknown. To understand the function of VPS45 in vivo , we performed a genetic suppressor screen in Caenorhabditis elegans . We found that the temperature-sensitive lethality caused by the loss of VPS-45 can be suppressed by a mutation in another SM protein, VPS33A. The VPS33A M376I mutation is located in domain 3a, which is predicted to be essential for SNARE complex assembly...
2024: microPublication. Biology
#27
JOURNAL ARTICLE
Stella-Amrei Kunde, Bettina Schmerl, Judith von Sivers, Elham Ahmadyar, Taanisha Gupta, Nils Rademacher, Hanna L Zieger, Sarah A Shoichet
Synapse formation depends on the coordinated expression and regulation of scaffold proteins. The JNK family kinases play a role in scaffold protein regulation, but the nature of this functional interaction in dendritic spines requires further investigation. Here, using a combination of biochemical methods and live-cell imaging strategies, we show that the dynamics of the synaptic scaffold molecule SAP102 are negatively regulated by JNK inhibition, that SAP102 is a direct phosphorylation target of JNK3, and that SAP102 regulation by JNK is restricted to neurons that harbour mature synapses...
April 4, 2024: Journal of Biological Chemistry
#28
JOURNAL ARTICLE
Margaret S Robinson, Robin Antrobus, Anneri Sanger, Alexandra K Davies, David C Gershlick
The AP-1 adaptor complex is found in all eukaryotes, but it has been implicated in different pathways in different organisms. To look directly at AP-1 function, we generated stably transduced HeLa cells coexpressing tagged AP-1 and various tagged membrane proteins. Live cell imaging showed that AP-1 is recruited onto tubular carriers trafficking from the Golgi apparatus to the plasma membrane, as well as onto transferrin-containing early/recycling endosomes. Analysis of single AP-1 vesicles showed that they are a heterogeneous population, which starts to sequester cargo 30 min after exit from the ER...
July 1, 2024: Journal of Cell Biology
#29
JOURNAL ARTICLE
R J Mulligan, M M Magaj, L Digilio, S Redemann, C C Yap, B Winckler
Endosomal-lysosomal trafficking is accompanied by the acidification of endosomal compartments by the H+-V-ATPase to reach low lysosomal pH. Disruption of proper pH impairs lysosomal function and the balance of protein synthesis and degradation (proteostasis). We used the small dipeptide LLOMe, which is known to permeabilize lysosomal membranes, and find that LLOMe also impacts late endosomes (LEs) by neutralizing their pH without causing membrane permeabilization. We show that LLOMe leads to hyper-activation of Rab7 and disruption of tubulation and mannose-6-phosphate receptor (CI-M6PR) recycling on pH-neutralized LEs...
April 5, 2024: Journal of Cell Science
#30
REVIEW
Damilare Emmanuel Rotimi, Matthew Iyobhebhe, Elizabeth Temidayo Oluwayemi, Ikponmwosa Owen Evbuomwan, Rotdelmwa Maimako Asaleye, Oluwafemi Adeleke Ojo, Oluyomi Stephen Adeyemi
The mitophagy process, a type of macroautophagy, is the targeted removal of mitochondria. It is a type of autophagy exclusive to mitochondria, as the process removes defective mitochondria one by one. Mitophagy serves as an additional level of quality control by using autophagy to remove superfluous mitochondria or mitochondria that are irreparably damaged. During spermatogenesis, mitophagy can influence cell homeostasis and participates in a variety of membrane trafficking activities. Crucially, it has been demonstrated that defective mitophagy can impede spermatogenesis...
July 2024: Biochemistry and Biophysics Reports
#31
REVIEW
Yao Lu, Ke Cheng, Hui Tang, Jinyan Li, Chunjiao Zhang, Hongliang Zhu
Small GTPase is a type of crucial regulator in eukaryotes. It acts as a molecular switch by binding with GTP and GDP in cytoplasm, affecting various cellular processes. Small GTPase were divided into five subfamilies based on sequence, structure and function: Ras, Rho, Rab, Arf/Sar and Ran, with Rab being the largest subfamily. Members of the Rab subfamily play an important role in regulating complex vesicle transport and microtubule system activity. Plant cells are composed of various membrane-bound organelles, and vesicle trafficking is fundamental to the existence of plants...
March 30, 2024: Journal of Plant Physiology
#32
JOURNAL ARTICLE
Eric M Rosenberg, Xiaoying Jian, Olivier Soubias, Rebekah A Jackson, Erin Gladu, Emily Andersen, Lothar Esser, Alexander J Sodt, Di Xia, R Andrew Byrd, Paul A Randazzo
The ADP-ribosylation factors (Arfs) constitute a family of small GTPases within the Ras superfamily, with a distinguishing structural feature of a hypervariable N-terminal extension of the G domain modified with myristate. Arf proteins, including Arf1, have roles in membrane trafficking and cytoskeletal dynamics. While screening for Arf1:small molecule co-crystals, we serendipitously solved the crystal structure of the non-myristoylated engineered mutation [L8K]Arf1 in complex with a GDP analogue. Like wild-type (WT) non-myristoylated Arf1•GDP, we observed that [L8K]Arf1 exhibited an N-terminal helix that occludes the hydrophobic cavity that is occupied by the myristoyl group in the GDP-bound state of the native protein...
2024: PloS One
#33
Hussein Algahtani, Bader Shirah, Muhammad Imran Naseer
Vacuolar protein sorting 13 homolog D (VPS13D) gene encodes a protein involved in trafficking of membrane proteins between the trans-Golgi network and the prevacuolar compartment. This study reports a novel homozygous mutation (c.12494T>C p.Ile4165Thr) in the VPS13D gene in a Saudi female diagnosed with autosomal recessive spinocerebellar ataxia type 4 (SCAR4). The patient's clinical presentation, including progressive weakness, ataxia, and numbness, aligns with SCAR4 characteristics. The comprehensive evaluation, comprising neurological examination, brain MRI, and genetic testing, revealed distinctive features consistent with autosomal recessive inheritance...
March 30, 2024: Clinical Neurology and Neurosurgery
#34
JOURNAL ARTICLE
Sasmita Pradhan, Lipika Mirdha, Tanusree Sengupta, Hirak Chakraborty
The apolipoprotein E (ApoE) signal peptide is a short stretch of N-terminal amino acids that direct the ApoE protein to the endoplasmic reticulum after synthesis. Previous studies have shown that this peptide can bind to lipid membranes in a cholesterol-dependent manner; however, the mechanism of this interaction is yet to be clarified. In this study, we aimed to investigate how the composition of neighboring lipids affects the membrane-binding of the ApoE signal peptide. We found that a negatively charged lipid, such as phosphatidylglycerol, can act as a switch that reduces the binding efficiency of the peptide to cholesterol-rich membranes...
April 3, 2024: Langmuir: the ACS Journal of Surfaces and Colloids
#35
JOURNAL ARTICLE
Lucia Pedicini, Jessica Smith, Sinisa Savic, Lynn McKeown
Mast cells are infamous for mediating allergic and inflammatory diseases due to their capacity of rapidly releasing a wide range of inflammatory mediators stored in cytoplasmic granules. However, mast cells also have several important physiological roles that involve selective and agonist-specific release of these active mediators. While a filtering mechanism at the plasma membrane could regulate the selective release of some cargo, the plethora of stored cargo and the diversity of mast cell functions suggests the existence of granule subtypes with distinct trafficking pathways...
2024: Discov Immunol
#36
JOURNAL ARTICLE
Jingru Wang, Juan Xiong, Shuhan Zhang, Dongchen Li, Qingzhu Chu, Weiping Chang, Lin Deng, Wei-Ke Ji
Early endosomes (EEs) are crucial in cargo sorting within vesicular trafficking. While cargoes destined for degradation are retained in EEs and eventually transported to lysosomes, recycled cargoes for the plasma membrane (PM) or the Golgi undergo segregation into specialized membrane structures known as EE buds during cargo sorting. Despite this significance, the molecular basis of the membrane expansion during EE bud formation has been poorly understood. In this study, we identify a protein complex comprising SHIP164, an ATPase RhoBTB3, and a retromer subunit Vps26B, which promotes the formation of EE buds at Golgi-EE contacts...
April 2, 2024: Cell Discovery
#37
REVIEW
Jorge Román Corona-Rivera, Iván Martínez-Duncker, Eva Morava, Wasantha Ranatunga, Roberta Salinas-Marin, Ana María González-Jaimes, Katia Alejandra Castillo-Reyes, Christian Peña-Padilla, Lucina Bobadilla-Morales, Alfredo Corona-Rivera, Mireya Orozco-Vela, Sinhue Alejandro Brukman-Jiménez
The trafficking protein particle (TRAPP) complex is a multisubunit protein complex that functions as a tethering factor involved in intracellular trafficking. TRAPPC11, a crucial subunit of this complex, is associated with pathogenic variants that cause a spectrum of disease, which can range from a limb girdle muscular dystrophy (LGMD) to developmental disability with muscle disease, movement disorder and global developmental delay (GDD)/intellectual disability (ID), or even a congenital muscular dystrophy (CMD)...
March 28, 2024: Molecular Genetics and Metabolism
#38
Alix Thomas, Braden Lobingier, Carsten Schultz, Aurelien Laguerre
G protein-coupled receptors (GPCRs) are membrane bound signaling molecules that regulate many aspects of human physiology. Recent advances have demonstrated that GPCR signaling can occur both at the cell surface and internal cellular membranes. Our findings suggest that cannabinoid receptor 1 (CB1) signaling is highly dependent on its subcellular location. We find that intracellular CB1 receptors predominantly couple to Gαi while plasma membrane receptors couple to Gαs. Here we show subcellular location of CB1, and its signaling, is contingent on the choice of promoters and receptor tags...
March 22, 2024: bioRxiv
#39
Rizwan Romee, Shaobo Yang, Michal Sheffer, Isabel Kaplan, Zongqi Wang, Mubin Tarannum, Khanhlinh Dinh, Yasmin Abdulhamid, Roman Shapiro, Rebecca Porter, Robert Soiffer, Jerome Ritz, John Koreth, Yun Wei, Peiru Chen, Ke Zhang, Valeria Márquez-Pellegrin, Shanna Bonanno, Neel Joshi, Ming Guan, Mengdi Yang, Deng Li, Chiara Bellini, Jianzhu Chen, Catherine Wu, David Barbie, Jiahe Li
Given the safety, tumor tropism, and ease of genetic manipulation in non-pathogenic Escherichia coli ( E. coli ), we designed a novel approach to deliver biologics to overcome poor trafficking and exhaustion of immune cells in the tumor microenvironment, via the surface display of key immune-activating cytokines on the outer membrane of E. coli K-12 DH5α. Bacteria expressing murine decoy-resistant IL18 mutein (DR18) induced robust CD8 + T and NK cell-dependent immune responses leading to dramatic tumor control, extending survival, and curing a significant proportion of immune-competent mice with colorectal carcinoma and melanoma...
March 22, 2024: Research Square
#40
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
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