Article
Biochemistry & Molecular Biology
Thibault Courtellemont, Maria Giovanna De Leo, Navin Gopaldass, Andreas Mayer
Summary: Endo-lysosomal compartments exchange proteins through different processes, including fusion, fission, and endosomal transport carriers. The membrane fission events that occur during these processes are not well understood. This study identifies the CROP complex as a factor that plays a role in membrane fission. The CROP complex consists of members from two protein families and enhances the membrane fission activity of a specific protein. Disrupting the CROP complex prevents fragmentation of lysosome-like structures in yeast and impairs cargo export in mammalian endosomes.
Review
Cell Biology
Liriope Toupenet Marchesi, Marion Leblanc, Giovanni Stevanin
Summary: Hereditary spastic paraplegia (HSP) involves the degeneration of motor neurons and is characterized by clinical and genetic heterogeneity, making it challenging to find effective therapies. Several HSP genes/proteins are linked to the endolysosomal and autophagic pathways, suggesting a functional convergence, which may have implications for understanding the pathological mechanisms of HSP.
Review
Biochemistry & Molecular Biology
Amitha Muraleedharan, Benoit Vanderperre
Summary: Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease, and its prevalence increases with age. The endolysosomal system plays a major role in the pathogenesis of PD, and studying the genes and proteins involved in this system can lead to potential therapeutic interventions.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Navin Gopaldass, Maria Giovanna De Leo, Thibault Courtellemont, Vincent Mercier, Christin Bissig, Aurelien Roux, Andreas Mayer
Summary: Proteins exit from endosomes through retromer-coated tubular carriers, which affects cellular signaling, lysosomal biogenesis, and various diseases. The coat formation requires overcoming membrane tension. In this study, we investigated the dynamics and driving force of this process using yeast retromer, BAR-domain sorting nexins Vps5 and Vps17, and synthetic lipid tubules. The results showed that the coat forms a static tubular structure by bidirectional oligomerization, and high concentrations of sorting nexins constrict the membrane tubes. However, retromer oligomers are needed to drive constriction at lower concentrations.
Article
Biochemistry & Molecular Biology
Elisabet Uribe-Carretero, Guadalupe Martinez-Chacon, Sokhna M. S. Yakhine-Diop, Gema Duque-Gonzalez, Mario Rodriguez-Arribas, Eva Alegre-Cortes, Marta Paredes-Barquero, Saray Canales-Cortes, Elisa Pizarro-Estrella, Antonio Cuadrado, Rosa Ana Gonzalez-Polo, Jose M. Fuentes, Mireia Niso-Santano
Summary: KEAP1 is an adaptor protein that plays an important role in regulating protein degradation. Loss of KEAP1 leads to protein oxidative aggregation and defective autophagy. Our study demonstrates that KEAP1 deficiency affects the endosome-lysosomal pathway, resulting in downregulation of cathepsin D and accumulation of autophagosomes.
Article
Cell Biology
Eva Alegre-Cortes, Alberto Gimenez-Bejarano, Elisabet Uribe-Carretero, Marta Paredes-Barquero, Andre R. A. Marques, Mafalda Lopes-da-Silva, Otilia V. Vieira, Saray Canales-Cortes, Pedro J. Camello, Guadalupe Martinez-Chacon, Ana Aiastui, Roberto Fernandez-Torron, Adolfo Lopez de Munain, Patricia Gomez-Suaga, Mireia Niso-Santano, Rosa A. Gonzalez-Polo, Jose M. Fuentes, Sokhna M. S. Yakhine-Diop
Summary: Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase gene. Fibroblasts derived from DM1 patients show increased autophagy flux, enlarged endosomes, and lysosomes. The binding of EGF to EGFR and the internalization of EGFR are delayed in DM1 cells, but EGF-activated EGFR enhances the phosphorylation of AKT and ERK1/2.
Review
Biochemistry & Molecular Biology
C. Alexander Boecker
Summary: This review summarizes the role of LRRK2 in intracellular organelle dynamics, focusing on its effects on microtubule function, mitochondrial dynamics, the autophagy-lysosomal pathway, and synaptic vesicle trafficking. It highlights our current understanding of how intracellular dynamics are altered upon pathogenic LRRK2 hyperactivation.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Review
Neurosciences
Saffire H. Krance, Che-Yuan Wu, Alison C. Y. Chan, Stephanie Kwong, Bing Xin Song, Lisa Y. Xiong, Michael Ouk, Ming Hui Chen, Jane Zhang, Adrian Yung, Meagan Stanley, Nathan Herrmann, Krista L. Lanctot, Walter Swardfager
Summary: Differences in endosomal-lysosomal and autophagy proteins were observed in the cerebrospinal fluid (CSF) of individuals with Alzheimer's disease compared to healthy controls. This suggests that dysregulation of these proteins may play a role in the pathogenesis of Alzheimer's disease.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Marijn Kuijpers, Domenico Azarnia Tehran, Volker Haucke, Tolga Soykan
Summary: Neurons present special challenges to the autophagy and endolysosomal systems due to their complex morphology and longevity. These systems play crucial roles in degrading defective proteins, maintaining cellular homeostasis, and participating in signaling in neurons, especially in axons.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Immunology
Zhenfeng Wang, Jiadi Lv, Pin Yu, Yajin Qu, Yabo Zhou, Li Zhou, Qiangqiang Zhu, Shunshun Li, Jiangping Song, Wei Deng, Ran Gao, Yuying Liu, Jiangning Liu, Wei-Min Tong, Chuan Qin, Bo Huang
Summary: The study demonstrates the potential therapeutic effect of ACE2-overexpressing A549 cell-derived microparticles (AO-MPs) against SARS-CoV-2 infection by changing endosomal pH and promoting viral degradation. In addition to inhibiting the inflammatory response of alveolar macrophages, AO-MPs increase treatment efficacy in a SARS-CoV-2-infected mouse model without side effects, highlighting the potential use of AO-MPs in treating SARS-CoV-2-infected patients and the feasibility of microparticle therapies for combating emerging respiratory viruses in the future.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Toxicology
Kei Takahashi, Yasuhiro Morita, Shuji Udagawa, Eriko Higashi, Mayumi Nakajima, Yohei Miyamoto, Keiyu Oshida
Summary: A research conducted overseas found that a drug called DMIP induces cell death and vacuolation in human aortic vascular smooth muscle cells. The vacuolation is caused by the accumulation of DMIP in the cells, and can be significantly reduced by using a vacuolar H+- ATPase inhibitor. The study also suggests that these vacuoles are mainly enlarged late endosomes/lysosomes, and not formed through autophagy.
TOXICOLOGY IN VITRO
(2023)
Review
Cell Biology
Dipen Rajgor, Theresa M. Welle, Katharine R. Smith
Summary: Neurons exhibit a high degree of compartmentalization, with localized protein synthesis at synaptic sites being essential for synaptic plasticity. Coordinated mechanisms involving RNA trafficking and mitochondrial fueling of synaptic translation are crucial for regulating activity-dependent protein synthesis and modulating synaptic strength.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Adenrele M. Gleason, Elizabeth G. Woo, Cindy McKinney, Ellen Sidransky
Summary: Exosomes, small organelles formed from endosomal membranes, serve as heterogeneous sources of biological and pathological biomarkers that capture the metabolic status of a cell. They can act as messengers between different cell types in the central nervous system. The content of exosomes is unique to each lysosomal storage disorder, and understanding their function may have therapeutic implications.
Article
Multidisciplinary Sciences
Julio Madrigal-Matute, Jenny de Bruijn, Kim van Kuijk, Dario F. Riascos-Bernal, Antonio Diaz, Inmaculada Tasset, Adrian Martin-Segura, Marion J. J. Gijbels, Bianca Sander, Susmita Kaushik, Erik A. L. Biessen, Simoni Tiano, Mathieu Bourdenx, Gregory J. Krause, Ian McCracken, Andrew H. Baker, Han Jin, Nicholas E. S. Sibinga, Jose Javier Bravo-Cordero, Fernando Macian, Rajat Singh, Patrick C. N. Rensen, Jimmy F. P. Berbee, Gerard Pasterkamp, Judith C. Sluimer, Ana Maria Cuervo
Summary: The study found that reduced activity of chaperone-mediated autophagy (CMA) exacerbates the progression of atherosclerosis. Conversely, up-regulated CMA in a genetic mouse model leads to lower vulnerability to atherosclerotic challenges. Thus, CMA could be an attractive therapeutic target against cardiovascular diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Xiangyu Huang, Guihu Yin, Bin Zhou, Yiqin Cai, Jianing Hu, Jingwen Huang, Zili Chen, Qingtao Liu, Xiuli Feng
Summary: This study investigates the role of Keratin10 in the infection and replication of avian influenza virus (AIV). It was found that Keratin10 interacts with the viral NS2 protein and plays a critical role in viral transport and offspring virus generation. Knocking down Keratin10 leads to trapped AIV particles and increased acidity in endosomes and lysosomes, inhibiting viral fusion and uncoating.
VETERINARY MICROBIOLOGY
(2023)
Article
Hematology
Abigail S. Haka, Rajesh K. Singh, Inna Grosheva, Haley Hoffner, Estibaliz Capetillo-Zarate, Harvey F. Chin, Niroshana Anandasabapathy, Frederick R. Maxfield
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2015)
Article
Biochemistry & Molecular Biology
David B. Iaea, Igor Dikiy, Irene Kiburu, David Eliezer, Frederick R. Maxfield
Review
Biochemistry & Molecular Biology
David B. Iaea, Frederick R. Maxfield
MEMBRANE NANODOMAINS
(2015)
Article
Biochemistry & Molecular Biology
David B. Iaea, Sarah E. Gale, Agata A. Bielska, Kathiresan Krishnan, Hideji Fujiwara, Hui Jiang, Frederick R. Maxfield, Paul H. Schlesinger, Douglas F. Covey, Jean E. Schaffer, Daniel S. Ory
JOURNAL OF LIPID RESEARCH
(2015)
Article
Neurosciences
Maria Praggastis, Brett Tortelli, Jessie Zhang, Hideji Fujiwara, Rohini Sidhu, Anita Chacko, Zhouji Chen, Chan Chung, Andrew P. Lieberman, Jakub Sikora, Cristin Davidson, Steven U. Walkley, Nina H. Pipalia, Frederick R. Maxfield, Jean E. Schaffer, Daniel S. Ory
JOURNAL OF NEUROSCIENCE
(2015)
Review
Cell Biology
Santiago Sole-Domenech, Dana L. Cruz, Estibaliz Capetillo-Zarate, Frederick R. Maxfield
AGEING RESEARCH REVIEWS
(2016)
Article
Biochemistry & Molecular Biology
Abigail S. Haka, Valeria C. Barbosa-Lorenzi, Hyuek Jong Lee, Domenick J. Falcone, Clifford A. Hudis, Andrew J. Dannenberg, Frederick R. Maxfield
JOURNAL OF LIPID RESEARCH
(2016)
Article
Biochemistry & Molecular Biology
Nina H. Pipalia, Kanagaraj Subramanian, Shu Mao, Harold Ralph, Darren M. Hutt, Samantha M. Scott, William E. Balch, Frederick R. Maxfield
JOURNAL OF LIPID RESEARCH
(2017)
Article
Chemistry, Medicinal
Jayendra Z. Patel, Tapio J. Nevalainen, Juha R. Savinainen, Yahaya Adams, Tuomo Laitinen, Robert S. Runyon, Miia Vaara, Stephen Ahenkorah, Agnieszka A. Kaczor, Dina Navia-Paldanius, Mikko Gynther, Niina Aaltonen, Amit A. Joharapurkar, Mukul R. Jain, Abigail S. Haka, Frederick R. Maxfield, Jarmo T. Laitinen, Teija Parkkari
Editorial Material
Biology
Kevin C. Courtney, Karen Y. Y. Fung, Frederick R. Maxfield, Gregory D. Fairn, Xiaohui Zha
Article
Cell Biology
Rajesh K. Singh, Frederik W. Lund, Abigail S. Haka, Frederick R. Maxfield
JOURNAL OF CELL SCIENCE
(2019)
Review
Cell Biology
Frederick R. Maxfield, Valeria C. Barbosa-Lorenzi, Rajesh K. Singh
Article
Biochemistry & Molecular Biology
Xiaoxue Zhang, Hengyi Xie, David Iaea, George Khelashvili, Harel Weinstein, Frederick R. Max
Summary: This study demonstrates a PIP-selective mechanism by which the protein StarD4 extracts cholesterol from liposomes. The lipid composition of the donor and acceptor membranes plays a role in modulating StarD4-mediated transport. Molecular dynamics simulations reveal the key interaction sites of StarD4 with PIP-containing membranes. These findings provide insights into the mechanism by which PIPs regulate cholesterol transfer activity via StarD4.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Neurosciences
Shayri G. Greenwood, Laura Montroull, Marta Volosin, Helen E. Scharfman, Kenneth K. Teng, Matthew Light, Risa Torkin, Fredrick Maxfield, Barbara L. Hempstead, Wilma J. Friedman
Meeting Abstract
Biochemistry & Molecular Biology
Fred Maxfield