Article
Cell Biology
Jake Cross, Joanne Durgan, David G. McEwan, Matthew Tayler, Kevin M. Ryan, Oliver Florey
Summary: Cross et al. demonstrate that non-canonical autophagy activation is responsible for the majority of ATG8 lipidation in response to lysosome damage, rather than lysophagy. They show that ATG8 proteins directly conjugate to lysosomal membranes and interact with the lipid transfer protein ATG2. This study reveals a parallel ATG8 response to lysosome damage that is mechanistically distinct from lysophagy and involves important links to lipid transfer and dynamics.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Bhairavi Tolani, Anna Celli, Yanmin Yao, Yong Zi Tan, Richard Fetter, Christina R. Liem, Adam J. de Smith, Thamiya Vasanthakumar, Paola Bisignano, Adam D. Cotton, Ian B. Seiple, John L. Rubinstein, Marco Jost, Jonathan S. Weissman
Summary: The study discovered a cytotoxic agent, 249C, that selectively targets Ras-mutant cancer cells and effectively inhibits tumor growth, offering a potential therapeutic strategy for cancers driven by specific KRAS mutations.
NATURE BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Longfei Wang, Di Wu, Carol Robinson, Tian-Min Fu
Summary: This study identifies a new protein called mEAK-7 that interacts with V-ATPases and may regulate its function while also being involved in mTOR signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Annie Lauzier, Marie-France Bossanyi, Raphaelle Larcher, Sonya Nassari, Rupali Ugrankar, W. Mike Henne, Steve Jean
Summary: This study identifies a conserved role for Snz/SNX25 as a regulator of autophagic flux and reveals differential isoform expression between paralogs.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biology
Maria Podinovskaia, Cristina Prescianotto-Baschong, Dominik P. Buser, Anne Spang
Summary: This study introduces a novel live-cell imaging assay for monitoring endosome maturation process, applicable to various types of mammalian cells. It was found that different endosome conversion processes and acidification relied on different factors. This assay serves as a powerful tool to further unravel various aspects of endosome maturation.
Review
Cell Biology
Markus Ritter, Nikolaus Bresgen, Hubert H. Kerschbaum
Summary: The volumes of cells and their organelles are regulated by osmoregulatory processes. Cells respond to osmotic gradients by adjusting their volume, while cell death pathways can lead to either a decrease or increase in cell volume. Dysfunction in pinocytosis and macropinocytosis can result in cell swelling and fluid accumulation, ultimately leading to cell death.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Gareth Griffiths, Jean Gruenberg, Mark Marsh, Jens Wohlmann, Arwyn T. Jones, Robert G. Parton
Summary: Nanoparticles are promising for delivering drugs, proteins, and nucleic acids into cells. The development and application of nanoparticles involve scientists from various fields who design, fabricate, and characterize nanoparticles in vitro. However, the research on the interactions between nanoparticles and cells in the field of cell biology is often of sub-standard quality.
ADVANCED DRUG DELIVERY REVIEWS
(2022)
Review
Cell Biology
Johannes Westman, Sergio Grinstein
Summary: The ability of phagosomes to halt microbial growth is closely linked to their ability to acidify their luminal pH, but certain pathogens can survive and replicate inside phagosomes by targeting the pH-regulatory machinery of host cells to survive or escape.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Anh Hoang Le, Tamas Yelland, Nikki R. Paul, Loic Fort, Savvas Nikolaou, Shehab Ismail, Laura M. Machesky
Summary: The study reveals that CYRI-A is a key regulator of macropinosome formation and integrin internalization, being transiently recruited to nascent macropinosomes and dependent on PI3K and RAC1 activity for its function.
JOURNAL OF CELL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Vladimir Marshansky
Summary: This review discusses the history of discovery and study of the two rotary ion-translocating ATPase nano-motors, focusing on their functioning in bacteria, eukaryotic cells and animal mitochondria. It highlights the common evolutionary origin of these nano-motors built into cell membranes that was invented by Nature billions of years ago.
BIOCHEMISTRY-MOSCOW
(2022)
Review
Multidisciplinary Sciences
Joanne Durgan, Oliver Florey
Summary: Autophagy is a fundamental catabolic process coordinated by a network of autophagy-related proteins. The noncanonical autophagy pathway, which utilizes the same proteins, plays a crucial role in immunity, inflammation, cancer, and neurodegeneration. This review discusses the various stimuli and processes involved in noncanonical autophagy, as well as the molecular features of the associated pathways. The authors propose an updated and unified mechanism for noncanonical autophagy.
Article
Biochemistry & Molecular Biology
Paul R. C. Imbert, Amra Saric, Kayvon Pedram, Carolyn R. Bertozzi, Sergio Grinstein, Spencer A. Freeman
Summary: The study reveals the physical barriers that modulate phagocytosis, showing that the coating of glycosaminoglycans and glycoproteins on phagocytic targets, as well as self-synthesized or acquired glycocalyx components on macrophages, hinder phagocytosis by steric and electrostatic means. Enzymatic removal of these barriers significantly enhances phagocytic efficiency, with particular emphasis on the clearance of mucins in cancer cells.
Article
Genetics & Heredity
Lin Wang, Dominik Aschenbrenner, Zhiyang Zeng, Xiya Cao, Daniel Mayr, Meera Mehta, Melania Capitani, Neil Warner, Jie Pan, Liren Wang, Qi Li, Tao Zuo, Sarit Cohen-Kedar, Jiawei Lu, Rico Chandra Ardy, Daniel J. Mulder, Dilan Dissanayake, Kaiyue Peng, Zhiheng Huang, Xiaoqin Li, Yuesheng Wang, Xiaobing Wang, Shuchao Li, Samuel Bullers, Anis N. Gammage, Klaus Warnatz, Ana-Iris Schiefer, Gergely Krivan, Vera Goda, Walter H. A. Kahr, Mathieu Lemaire, Chien-Yi Lu, Iram Siddiqui, Michael G. Surette, Daniel Kotlarz, Karin R. Engelhardt, Helen R. Griffin, Robert Rottapel, Helene Decaluwe, Ronald M. Laxer, Michele Proietti, Sophie Hambleton, Suzanne Elcombe, Cong-Hui Guo, Bodo Grimbacher, Iris Dotan, Siew C. Ng, Spencer A. Freeman, Scott B. Snapper, Christoph Klein, Kaan Boztug, Ying Huang, Dali Li, Holm H. Uhlig, Aleixo M. Muise
Summary: The study identified damaging SYK gain-of-function variants in patients with immune deficiency and inflammatory diseases, which could be treated with bone marrow transplantation or SYK inhibitors. Treatment strategies for patients with SYK mutations were highlighted through knock-in mouse models showing disease amelioration with these interventions.
Review
Cell Biology
Spencer Freeman, Sergio Grinstein
Summary: Phagocytosis is finely tuned by developmental and environmental factors, with key determinants being regulated via transcriptional and epigenetic means. Membrane traffic, cytoskeleton, and signaling control activation of phagocytic receptors, while the coexistence of various eat-me and don't-eat-me signals adds complexity to the process.
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 37
(2021)
Review
Cell Biology
Sarah R. Chadwick, Sergio Grinstein, Spencer A. Freeman
Summary: The role of specific proteins and lipids in endocytic traffic has been extensively studied, but little is known about the contribution of endocytic fluid to these events. Experimental findings suggest an intimate association between luminal ions, their transport, and endocytic traffic, but mechanisms for how cells sense inorganic ions and transmit this information remain largely unknown.
CURRENT OPINION IN CELL BIOLOGY
(2021)
Article
Oncology
Arif A. Arif, Yu-Hsuan Huang, Spencer A. Freeman, Jawairia Atif, Pamela Dean, Jacqueline C. Y. Lai, Marie-Renee Blanchet, Kimberly C. Wiegand, Kelly M. McNagny, T. Michael Underhill, Michael R. Gold, Pauline Johnson, Calvin D. Roskelley
Summary: Inflammation-induced monocyte-derived macrophages (MoDM) and hepatocyte growth factor (HGF) have been found to increase the formation of early micrometastatic lesions in the lung, enhancing the survival rate of tumor cells.
MOLECULAR CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Amra Saric, Spencer A. Freeman, Chad D. Williamson, Michal Jarnik, Carlos M. Guardia, Michael S. Fernandopulle, David C. Gershlick, Juan S. Bonifacino
Summary: Endolysosomes are tethered to the endoplasmic reticulum (ER) by the sorting nexin SNX19, reducing their motility and concentrating them in the perinuclear area. This mechanism involves specific protein domains and contributes to the regulation of organelle dynamics.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sina Ghasempour, Spencer A. Freeman
Summary: In order for tumors to establish malignant lesions, they must first evade detection by immune cells. They do this by modifying their glycocalyx, a network of polysaccharides and glycosylated proteins that prevents immune cells from engulfing them and hides antigens from the immune system. The barriers imposed by the glycocalyx are both physical and linked to immune cell signaling pathways. Therapies have been developed to edit and dismantle the glycocalyx barrier in order to enhance the immune response against tumors.
Article
Medicine, Research & Experimental
Gabriella Leung, Yuhuan Zhou, Philip Ostrowski, Sivakami Mylvaganam, Parastoo Boroumand, Daniel J. Mulder, Conghui Guo, Aleixo M. Muise, Spencer A. Freeman
Summary: The deficiency of ARPC1B can disrupt the nucleation of ARP2/3 complexes by WASP, affecting the cytoskeletal structures in B cells and macrophages, leading to increased tonic signaling in immune cells and impacting the threshold for activation in response to microbial-associated molecular patterns. This highlights the critical role of ARPC1B in controlling steady-state signaling of immune cells.
Article
Cell Biology
Sivakami Mylvaganam, Jonathan Plumb, Bushra Yusuf, Ren Li, Chien-Yi Lu, Lisa A. Robinson, Spencer A. Freeman, Sergio Grinstein
Summary: This study reveals the importance of the apical spectrin network in conveying shear forces to endothelial mechanosensors. Spectrins anchor CD44 to modulate the cell surface density of hyaluronan and translate shear into changes in plasma membrane tension. Spectrins also regulate the stability of apical caveolae, where the mechanosensitive PIEZO1 channels are thought to reside.
NATURE CELL BIOLOGY
(2022)
Article
Cell Biology
Samaneh Yazdani, Philip J. Bilan, Javier R. Jaldin-Fincati, Janice Pang, Felicia Ceban, Ekambir Saran, John H. Brumell, Spencer A. Freeman, Amira Klip
Summary: This study investigated the transport of glucose in human adipose tissue microvascular endothelial cells. The results showed that glucose was mainly taken up by glucose transporters GLUT1 and GLUT3 and a fraction of glucose was released from the cells. The study also found that a fluorescent glucose derivative entered the cells through endocytosis and was recycled back out.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Review
Physiology
Spencer A. Freeman, Sergio Grinstein, John Orlowski
Summary: The protonation state of macromolecules affects their properties and functions. Protons are also involved in metabolic reactions and drive the transmembrane transport of substances. Maintaining the intracellular pH is crucial for cellular stability. Recent advancements in molecular probes and genomic, proteomic, and electrophysiological techniques have enhanced our understanding of the regulation of intracellular pH and its implications for cellular function in health and disease.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Yusuke Hirata, Ruiqi Cai, Allen Volchuk, Benjamin E. Steinberg, Yoshiro Saito, Atsushi Matsuzawa, Sergio Grinstein, Spencer A. Freeman
Summary: The oxidizing lipid peroxides formed during ferroptosis accumulate at the plasma membrane, causing oxidation of surface membrane lipids and membrane tension. This activates Piezo1 and TRP channels, making the membrane permeable to cations such as Na+ and Ca2+ while losing K+. In addition, the oxidation of lipids depresses the activity of the Na+/K+-ATPase, further disrupting cation gradients. Overall, increased membrane permeability to cations is a critical step in the execution of ferroptosis.
Article
Cell Biology
Jing Ze Wu, Mariia Zeziulia, Whijin Kwon, Thomas J. Jentsch, Sergio Grinstein, Spencer A. Freeman
JOURNAL OF CELL BIOLOGY
(2023)
Article
Medicine, General & Internal
Chia Wei Teoh, Magdalena Riedl Khursigara, Carolina G. Ortiz-Sandoval, Jee Woo Park, Jun Li, Arlette Bohorquez-Hernandez, Valentina Bruno, Emily E. Bowen, Spencer A. Freeman, Lisa A. Robinson, Christoph Licht
Summary: This study found that the main mechanism of cyclosporine-induced thrombotic microangiopathy (TMA) is the decreased density of glycocalyx in endothelial cells, which leads to dysregulation of the complement system and promotes complement deposition and cytotoxicity. This finding provides a new therapeutic target and important marker for other secondary TMAs that have not been recognized to be complement-related.
FRONTIERS IN MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Sivakami Mylvaganam, Spencer A. Freeman, Sergio Grinstein
Summary: Cells of the innate immune system, such as macrophages, neutrophils, and dendritic cells, rely on dynamic membrane protrusions for essential antimicrobial and homeostatic functions. These protrusions, including pseudopodia, lamellipodia, and filopodia, facilitate the sampling and engulfment of surrounding fluid and particulates through mechanisms that involve extreme plasma membrane deformations and coordinated rearrangement of cytoskeletal polymers. This process ultimately leads to vacuolar compartments that undergo remodeling and resolution through cytoskeletal mechanisms.