keyword
https://read.qxmd.com/read/38287192/repurposing-an-endogenous-degradation-domain-for-antibody-mediated-disposal-of-cell-surface-proteins
#1
JOURNAL ARTICLE
Janika Schmitt, Emma Poole, Ian Groves, David J Owen, Stephen C Graham, John Sinclair, Bernard T Kelly
The exquisite specificity of antibodies can be harnessed to effect targeted degradation of membrane proteins. Here, we demonstrate targeted protein removal utilising a protein degradation domain derived from the endogenous human protein Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9). Recombinant antibodies genetically fused to this domain drive the degradation of membrane proteins that undergo constitutive internalisation and recycling, including the transferrin receptor and the human cytomegalovirus latency-associated protein US28...
January 29, 2024: EMBO Reports
https://read.qxmd.com/read/38272178/immunofluorescence-analysis-of-human-eosinophils
#2
JOURNAL ARTICLE
Sarah Almas, Nawell Fayad, Ojas Srivastava, Mujtaba Siddique, Sharanya Das, Nicolas Touret, Xuejun Sun, Paige Lacy
A prominent inflammatory cell type in allergic diseases is the eosinophil, a granulated white blood cell that releases pro-inflammatory cytokines. Eosinophil-derived cytokines, including interleukin-9 (IL-9) and interleukin-13 (IL-13), can skew the immune response towards an allergic phenotype. Unfortunately, it is challenging to immunolabel and collect quantifiable images of eosinophils given their innate autofluorescence and ability to nonspecifically bind to antibodies. Hence, it is important to optimize permeabilization, blocking, and imaging conditions for eosinophils...
January 23, 2024: Journal of Immunological Methods
https://read.qxmd.com/read/38247172/engineered-extracellular-vesicles-driven-by-erythrocytes-ameliorate-bacterial-sepsis-by-iron-recycling-toxin-clearing-and-inflammation-regulation
#3
JOURNAL ARTICLE
Yan Li, Guanlin Qu, Geng Dou, Lili Ren, Ming Dang, Huijuan Kuang, Lili Bao, Feng Ding, Guangzhou Xu, Zhiyuan Zhang, Chi Yang, Shiyu Liu
Sepsis poses a significant challenge in clinical management. Effective strategies targeting iron restriction, toxin neutralization, and inflammation regulation are crucial in combating sepsis. However, a comprehensive approach simultaneously targeting these multiple processes has not been established. Here, an engineered apoptotic extracellular vesicles (apoEVs) derived from macrophages is developed and their potential as multifunctional agents for sepsis treatment is investigated. The extensive macrophage apoptosis in a Staphylococcus aureus-induced sepsis model is discovered, unexpectedly revealing a protective role for the host...
January 21, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38217571/mechano-regulation-by-clathrin-pit-formation-and-passive-cholesterol-dependent-tubules-during-de-adhesion
#4
JOURNAL ARTICLE
Tithi Mandal, Arikta Biswas, Tanmoy Ghosh, Sreekanth Manikandan, Avijit Kundu, Ayan Banerjee, Dhrubaditya Mitra, Bidisha Sinha
Adherent cells ensure membrane homeostasis during de-adhesion by various mechanisms, including endocytosis. Although mechano-chemical feedbacks involved in this process have been studied, the step-by-step build-up and resolution of the mechanical changes by endocytosis are poorly understood. To investigate this, we studied the de-adhesion of HeLa cells using a combination of interference reflection microscopy, optical trapping and fluorescence experiments. We found that de-adhesion enhanced membrane height fluctuations of the basal membrane in the presence of an intact cortex...
January 13, 2024: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/38045054/sorting-nexin-3-exacerbates-doxorubicin-induced-cardiomyopathy-via-regulation-of-tfrc-dependent-ferroptosis
#5
JOURNAL ARTICLE
Wenjing Yu, Yuehuai Hu, Zhiping Liu, Kaiteng Guo, Dinghu Ma, Mingxia Peng, Yuemei Wang, Jing Zhang, Xiaolei Zhang, Panxia Wang, Jiguo Zhang, Peiqing Liu, Jing Lu
The clinical utilization of doxorubicin (Dox) in various malignancies is restrained by its major adverse effect: irreversible cardiomyopathy. Extensive studies have been done to explore the prevention of Dox cardiomyopathy. Currently, ferroptosis has been shown to participate in the incidence and development of Dox cardiomyopathy. Sorting Nexin 3 (SNX3), the retromer-associated cargo binding protein with important physiological functions, was identified as a potent therapeutic target for cardiac hypertrophy in our previous study...
December 2023: Acta Pharmaceutica Sinica. B
https://read.qxmd.com/read/37998376/examining-the-role-of-a-functional-deficiency-of-iron-in-lysosomal-storage-disorders-with-translational-relevance-to-alzheimer-s-disease
#6
REVIEW
Steven M LeVine
The recently presented Azalea Hypothesis for Alzheimer's disease asserts that iron becomes sequestered, leading to a functional iron deficiency that contributes to neurodegeneration. Iron sequestration can occur by iron being bound to protein aggregates, such as amyloid β and tau, iron-rich structures not undergoing recycling (e.g., due to disrupted ferritinophagy and impaired mitophagy), and diminished delivery of iron from the lysosome to the cytosol. Reduced iron availability for biochemical reactions causes cells to respond to acquire additional iron, resulting in an elevation in the total iron level within affected brain regions...
November 16, 2023: Cells
https://read.qxmd.com/read/37978880/the-endosomal-lysosomal-system-in-adc-design-and-cancer-therapy
#7
REVIEW
Jeffrey V Leyton
INTRODUCTION: This discourse delves into the intricate connections between the endosomal-lysosomal system and antibody-drug conjugates (ADCs), shedding light on an essential yet less understood dimension of targeted therapy. While ADCs have revolutionized cancer treatment, resistance remains a formidable challenge, often involving diverse and overlapping mechanisms. AREAS COVERED: This discourse highlights the roles of various components within the endosomal machinery, including Rab proteins, in ADC resistance development...
November 18, 2023: Expert Opinion on Biological Therapy
https://read.qxmd.com/read/37945025/iron-biology-an-overview-for-laboratorians
#8
REVIEW
William E Winter, Neil S Harris
Iron serves a critical role in many metabolic processes, including oxygen delivery (e.g., hemoglobin) and oxygen utilization for the generation of ATP (e.g., cytochromes). Disorders of iron metabolism are best recognized and evaluated in the context of iron's absorption, transportation, monitoring, cellular uptake, and recycling. This review highlights these processes so that disorders of iron deficiency and iron excess can be better understood. Key players in iron metabolism will be highlighted, such as hepcidin, ferroportin, erythroferrone, transferrin, ferritin, HFE, and the transferrin receptors...
September 2023: Annals of Clinical and Laboratory Science
https://read.qxmd.com/read/37942316/key-players-in-the-regulation-of-iron-homeostasis-at-the-host-pathogen-interface
#9
REVIEW
Inam Ullah, Minglin Lang
Iron plays a crucial role in the biochemistry and development of nearly all living organisms. Iron starvation of pathogens during infection is a striking feature utilized by a host to quell infection. In mammals and some other animals, iron is essentially obtained from diet and recycled from erythrocytes. Free iron is cytotoxic and is readily available to invading pathogens. During infection, most pathogens utilize host iron for their survival. Therefore, to ensure limited free iron, the host's natural system denies this metal in a process termed nutritional immunity...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37926552/ist1-regulates-select-recycling-pathways
#10
JOURNAL ARTICLE
Amy K Clippinger, Teresa V Naismith, Wonjin Yoo, Silvia Jansen, David J Kast, Phyllis I Hanson
ESCRTs (Endosomal Sorting Complex Required for Transports) are a modular set of protein complexes with membrane remodeling activities that include the formation and release of intraluminal vesicles (ILVs) to generate multivesicular endosomes. While most of the 12 ESCRT-III proteins are known to play roles in ILV formation, IST1 has been associated with a wider range of endosomal remodeling events. Here, we extend previous studies of IST1 function in endosomal trafficking and confirm that IST1, along with its binding partner CHMP1B, contributes to scission of early endosomal carriers...
November 5, 2023: Traffic
https://read.qxmd.com/read/37796517/chen-m-zhang-y-jiang-k-et%C3%A2-al-grab-regulates-transferrin-receptor-recycling-and-iron-uptake-in-developing-erythroblasts-blood-2022-140-10-1145-1155
#11
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
October 5, 2023: Blood
https://read.qxmd.com/read/37788328/%C3%AE-synuclein-induces-deficiency-in-clathrin-mediated-endocytosis-through-inhibiting-synaptojanin1-expression
#12
JOURNAL ARTICLE
Dong-Yan Song, Lin Yuan, Na Cui, Cong Feng, Lanxia Meng, Xin-He Wang, Man Xiang, Di Liu, Chun Wang, Zhentao Zhang, Jia-Yi Li, Wen Li
Parkinson's disease (PD) is an age-related chronic neurological disorder, mainly characterized by the pathological feature of α-synuclein (α-syn) aggregation, with the exact disease pathogenesis unclear. During the onset and progression of PD, synaptic dysfunction, including dysregulation of axonal transport, impaired exocytosis, and endocytosis are identified as crucial events of PD pathogenesis. It has been reported that over-expression of α-syn impairs clathrin-mediated endocytosis (CME) in the synapses...
November 2023: Journal of Neurochemistry
https://read.qxmd.com/read/37784954/the-ferroptosis-induced-by-palmitic-acid-via-cd36-activating-er-stress-to-break-calcium-iron-balance-in-colon-cancer-cells
#13
JOURNAL ARTICLE
H Kuang, T Li
PURPOSE/OBJECTIVE(S): There have been numerous studies to date on the treatment of tumors by saturated fatty acids. But the role that ferroptosis plays in this is not clear. Palmitic acid (PA) is a common saturated fatty acid with huge application prospects for inducing tumor cell ferroptosis. MATERIALS/METHODS: In vivo and in vitro experiments were performed to verify changes in cell proliferation, apoptosis and ferroptosis after PA treatment of colon cancer cells...
October 1, 2023: International Journal of Radiation Oncology, Biology, Physics
https://read.qxmd.com/read/37756124/p97-vcp-promotes-the-recycling-of-endocytic-cargo
#14
JOURNAL ARTICLE
Mona Kawan, Maria Körner, Andreas Schlosser, Alexander Buchberger
The endocytic pathway is of central importance for eukaryotic cells, as it enables uptake of extracellular materials, membrane protein quality control and recycling, as well as modulation of receptor signaling. While the ATPase p97 (VCP, Cdc48) has been found to be involved in the fusion of early endosomes and endolysosomal degradation, its role in endocytic trafficking is still incompletely characterized. Here, we identify myoferlin (MYOF), a ferlin family member with functions in membrane trafficking and repair, as a hitherto unknown p97 interactor...
September 27, 2023: Molecular Biology of the Cell
https://read.qxmd.com/read/37711075/biallelic-missense-variants-in-cog3-cause-a-congenital-disorder-of-glycosylation-with-impairment-of-retrograde-vesicular-trafficking
#15
JOURNAL ARTICLE
Ruizhi Duan, Dana Marafi, Zhi-Jie Xia, Bobby G Ng, Reza Maroofian, Farhana Taher Sumya, Ahmed K Saad, Haowei Du, Jawid M Fatih, Jill V Hunter, Hasnaa M Elbendary, Shahid M Baig, Uzma Abdullah, Zafar Ali, Stephanie Efthymiou, David Murphy, Tadahiro Mitani, Marjorie A Withers, Shalini N Jhangiani, Zeynep Coban-Akdemir, Daniel G Calame, Davut Pehlivan, Richard A Gibbs, Jennifer E Posey, Henry Houlden, Vladimir V Lupashin, Maha S Zaki, Hudson H Freeze, James R Lupski
Biallelic variants in genes for seven out of eight subunits of the conserved oligomeric Golgi complex (COG) are known to cause recessive congenital disorders of glycosylation (CDG) with variable clinical manifestations. COG3 encodes a constituent subunit of the COG complex that has not been associated with disease traits in human. Herein, we report two COG3 homozygous missense variants in four individuals from two unrelated consanguineous families that co-segregated with COG3-CDG. Clinical phenotypes of affected individuals include global developmental delay, severe intellectual disability, microcephaly, epilepsy, facial dysmorphism, and variable neurological findings...
September 15, 2023: Journal of Inherited Metabolic Disease
https://read.qxmd.com/read/37577466/ist1-regulates-select-endosomal-recycling-pathways
#16
Amy K Clippinger, Teresa V Naismith, Wonjin Yoo, Silvia Jansen, David J Kast, Phyllis I Hanson
ESCRTs (Endosomal Sorting Complex Required for Transport) are a modular set of protein complexes with membrane remodeling activities that include the formation and release of intralumenal vesicles (ILVs) to generate multivesicular endosomes. While most of the 12 ESCRT-III proteins are known to play roles in ILV formation, IST1 has been associated with a wider range of endosomal remodeling events. Here, we extend previous studies of IST1 function in endosomal trafficking and establish that IST1, along with its binding partner CHMP1B, contributes to scission of early endosomal carriers...
August 2, 2023: bioRxiv
https://read.qxmd.com/read/37324589/the-recurrent-pathogenic-pro890leu-substitution-in-cltc-causes-a-generalized-defect-in-synaptic-transmission-in-caenorhabditis-elegans
#17
JOURNAL ARTICLE
Luca Pannone, Valentina Muto, Francesca Nardecchia, Martina Di Rocco, Emilia Marchei, Federica Tosato, Stefania Petrini, Giada Onorato, Enrico Lanza, Lucia Bertuccini, Filippo Manti, Viola Folli, Serena Galosi, Elia Di Schiavi, Vincenzo Leuzzi, Marco Tartaglia, Simone Martinelli
De novo CLTC mutations underlie a spectrum of early-onset neurodevelopmental phenotypes having developmental delay/intellectual disability (ID), epilepsy, and movement disorders (MD) as major clinical features. CLTC encodes the widely expressed heavy polypeptide of clathrin, a major component of the coated vesicles mediating endocytosis, intracellular trafficking, and synaptic vesicle recycling. The underlying pathogenic mechanism is largely unknown. Here, we assessed the functional impact of the recurrent c...
2023: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/37192162/influenza-a-virus-exploits-transferrin-receptor-recycling-to-enter-host-cells
#18
JOURNAL ARTICLE
Beryl Mazel-Sanchez, Chengyue Niu, Nathalia Williams, Michael Bachmann, Hélèna Choltus, Filo Silva, Véronique Serre-Beinier, Wolfram Karenovics, Justyna Iwaszkiewicz, Vincent Zoete, Laurent Kaiser, Oliver Hartley, Bernhard Wehrle-Haller, Mirco Schmolke
Influenza A virus (IAV) enters host cells mostly through clathrin-dependent receptor-mediated endocytosis. A single bona fide entry receptor protein supporting this entry mechanism remains elusive. Here we performed proximity ligation of biotin to host cell surface proteins in the vicinity of attached trimeric hemagglutinin-HRP and characterized biotinylated targets using mass spectrometry. This approach identified transferrin receptor 1 (TfR1) as a candidate entry protein. Genetic gain-of-function and loss-of-function experiments, as well as in vitro and in vivo chemical inhibition, confirmed the functional involvement of TfR1 in IAV entry...
May 23, 2023: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/37088234/jian-pi-yi-shen-formula-restores-iron-metabolism-from-dysregulation-in-anemic-rats-with-adenine-induced-nephropathy
#19
JOURNAL ARTICLE
Changhui Li, Haipiao Huang, Rui Wang, Chi Zhang, Shiying Huang, Jinru Wu, Pingli Mo, Huimin Yu, Shunmin Li, Jianping Chen
ETHNOPHARMACOLOGICAL RELEVANCE: Jian-Pi-Yi-Shen (JPYS) is a herbal decoction being used to relieve the symptoms of chronic kidney disease (CKD) and its complications, including anemia, for over twenty years. Nonetheless, it is unclear how JPYS influences renal anemia and iron metabolism. AIM OF THE STUDY: An analysis of network pharmacology, chemical profiling, and in vivo experiments was conducted to identify the impact of JPYS on JAK2-STAT3 pathway and iron utilization in renal anemia and CKD...
April 21, 2023: Journal of Ethnopharmacology
https://read.qxmd.com/read/37002540/purification-analysis-intracellular-tracking-and-colocalization-of-extracellular-vesicles-using-atomic-force-and-3d-single-molecule-localization-microscopy
#20
JOURNAL ARTICLE
Sujitha Puthukodan, Martina Hofmann, Mario Mairhofer, Hannah Janout, Jonas Schurr, Fabian Hauser, Christoph Naderer, Johannes Preiner, Stephan Winkler, Dmitry Sivun, Jaroslaw Jacak
Extracellular vesicles (EVs) play a key role in cell-cell communication and thus have great potential to be utilized as therapeutic agents and diagnostic tools. In this study, we implemented single-molecule microscopy techniques as a toolbox for a comprehensive characterization as well as measurement of the cellular uptake of HEK293T cell-derived EVs (eGFP-labeled) in HeLa cells. A combination of fluorescence and atomic force microscopy revealed a fraction of 68% fluorescently labeled EVs with an average size of ∼45 nm...
March 31, 2023: Analytical Chemistry
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