Article
Biochemistry & Molecular Biology
Nicoletta Plotegher
Summary: Mitochondria, endoplasmic reticulum, and lysosomes play important roles in regulating pre-synaptic function. They can modulate ATP availability, control synaptic protein levels, and regulate Ca2+ signaling, which ultimately impact neuronal activity. The interplay between these organelles, either through signaling pathways or physical membrane contacts, needs to be considered when studying their impact on neurotransmission. This review discusses the physiological role of pre-synaptic organelles in neuronal function.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2023)
Editorial Material
Cell Biology
Hana Popelka, Daniel J. J. Klionsky
Summary: A recent study used cryo-electron tomography combined with computational analysis to gain insights into autophagosome biogenesis in yeast cells. This approach provided new information on autophagic structures, their contacts with organelles, membrane sources, and transition mechanisms. These findings open new avenues for autophagy research and highlight the potential of cryo-ET in cell biology.
Article
Multidisciplinary Sciences
Lauren C. Panzera, Ben Johnson, Josiah A. Quinn, In Ha Cho, Michael M. Tamkun, Michael B. Hoppa
Summary: Research indicates that Kv2.1 channels play a crucial role in facilitating ER calcium uptake during electrical activity in neurons, which is related to synaptic transmission. Loss of the Kv2.1 channel can disrupt synaptic vesicle fusion during stimulation, while its non-conducting role can link ER calcium uptake with electrical activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Nazmiye Ozkan, Max Koppers, Inge van Soest, Alexandra van Harten, Daphne Jurriens, Nalan Liv, Judith Klumperman, Lukas C. Kapitein, Casper C. Hoogenraad, Ginny G. Farias
Summary: This study demonstrates the role of endoplasmic reticulum (ER) tubules in regulating lysosome localization and function in neurons, by promoting lysosomal fission. These findings suggest that ER - lysosome inter-organelle membrane contact sites play a crucial role in determining lysosomal availability in axons.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Cell Biology
Annette C. Dolphin
Summary: Mueller et al. uncover distinct roles for Ca(V)1 and Ca(V)2 channels in neurotransmitter release at the C. elegans neuromuscular junction. Nanodomain coupling occurs via clustered Ca(V)2 channels, while release of a separate vesicular pool is mediated by more peripheral, dispersed Ca(V)1 channels, requiring obligatory coupling with RYR to amplify the Ca2+ signal.
Article
Oncology
Michael P. Ludwig, Matthew D. Galbraith, Neetha Paul Eduthan, Amanda A. Hill, Michael R. Clay, Cristiam Moreno Tellez, Breelyn A. Wilky, Anthony Elias, Joaquin M. Espinosa, Kelly D. Sullivan
Summary: Liposarcoma is a common soft-tissue sarcoma with potential therapeutic targets such as MDM2 and CDK4. This study focuses on the response of liposarcoma to the MDM2 inhibitor nutlin-3, and identifies the involvement of proteostasis network nodes in the mechanism. The combination of nutlin-3 and proteasome inhibitors shows promising apoptosis induction, with the ATF4/CHOP stress response axis playing a crucial role. Activation of the unfolded protein response enhances the efficacy of nutlin-3. In vivo models further confirm the synergistic effects of idasanutlin and carfilzomib in liposarcoma growth.
Article
Neurosciences
Vanessa Osman, Iris Speigel, Kishan Patel, Hugh C. Hemmings
Summary: Volatile anesthetics inhibit excitatory synaptic transmission by reducing presynaptic and postsynaptic Ca2+ concentrations. Ryanodine receptor 1 (RyR1) plays a key role in regulating intracellular Ca2+ and is a potential target for anesthetic action. Mutations in RyR1 are associated with malignant hyperthermia (MH) and can impact neuronal function. Volatile anesthetics decrease ER Ca2+ concentrations and synaptic vesicle exocytosis in both wild-type and mutant neurons, indicating that RyR1 may be involved in the effects of anesthetics on presynaptic Ca2+ handling.
Article
Reproductive Biology
Kangkang Gao, Yanyan Yi, Zhongqiang Xue, Zongjie Wang, Shan Huang, Beibei Zhang, Pengfei Lin, Aihua Wang, Huatao Chen, Yaping Jin
Summary: (XBP1s) is involved in several pathological processes in various organisms. This study aims to investigate the molecular mechanisms by which XBP1s mediates the inflammatory response in goat endometrial epithelial cells (gEECs) during lipopolysaccharide (LPS)-induced inflammation. The results suggest that XBP1s plays a crucial role in the regulation of inflammation in gEECs.
Review
Cell Biology
Satish Bodakuntla, Hana Nedozralova, Nirakar Basnet, Naoko Mizuno
Summary: Axon branching is a critical process for neural network formation, requiring a local system to dynamically control and regulate axonal growth. Regulation of axon branching involves coordination of cellular functions such as cytoskeleton and membrane remodeling.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Multidisciplinary Sciences
Masafumi Tsuboi, Yusuke Hirabayashi
Summary: Mammalian neurons are highly compartmentalized and require precise coordination of metabolic homeostasis and molecular composition in a compartment-specific manner. Recent studies have shown that the neuronal endoplasmic reticulum (ER) has compartment-specific structures and forms contacts with other membranes, such as mitochondria and the plasma membrane, but the functions of these contacts remain unclear.
PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES
(2021)
Article
Chemistry, Applied
Shane M. Hickey, Ian R. D. Johnson, Elena Dallerba, Mark J. Hackett, Massimiliano Massi, Joanna Lazniewska, Lauren A. Thurgood, Frederick M. Pfeffer, Douglas A. Brooks, Trent D. Ashton
Summary: We introduce a highly fluorescent, solvatochromic, 1,8-naphthalimide probe that enables the simultaneous imaging of lipid droplets and endoplasmic reticulum, with distinguishable emission maxima. By delineating organelles based on their emission profiles, we are able to visualize lipid droplet biogenesis and intercellular trafficking events. Furthermore, this probe demonstrates potential histochemical applications by staining myelin lipids in ex vivo brain tissue.
Article
Cell Biology
Bahnisikha Barman, Bong Hwan Sung, Evan Krystofiak, Jie Ping, Marisol Ramirez, Bryan Millis, Ryan Allen, Nripesh Prasad, Sergei Chetyrkin, M. Wade Calcutt, Kasey Vickers, James G. Patton, Qi Liu, Alissa M. Weaver
Summary: RNA-containing extracellular vesicles (EVs) are generated at endoplasmic reticulum membrane contact sites (ER MCSs), regulated by the ER MCS linker protein VAP-A. These VAP-A-regulated EVs play a critical role in miR-100 transfer between cells and tumor formation in vivo.
DEVELOPMENTAL CELL
(2022)
Review
Cell Biology
Nica Borgese, Nicola Iacomino, Sara Francesca Colombo, Francesca Navone
Summary: VAP proteins are essential adaptor proteins of the ER membrane that can recruit interacting partners, with mutations leading to familial ALS. Deficiency of VAPB affects various cell processes, potentially being the main driver of ALS pathogenesis.
Article
Cell Biology
Huaying Cai, Linhui Ni, Xingyue Hu, Xianjun Ding
Summary: This study illustrated the critical role of ER stress in synaptic plasticity and structural-functional alterations in a DYT1 dystonia mouse model, and found that ER stress inhibitor TUDCA could rescue the deficits.
Article
Biochemical Research Methods
Bahnisikha Barman, Marisol Ramirez, Toni Renee Dawson, Qi Liu, Alissa M. Weaver
Summary: Extracellular vesicles (EVs) play a role in cell functions through their protein, nucleic acid, and lipid cargoes. This study investigates the protein content of VAP-A-regulated EVs and reveals changes in RNA-related mechanisms and other functionally interacting protein networks.
Article
Cell Biology
Ivar Noordstra, Cyntha M. van den Berg, Fransje W. J. Boot, Eugene A. Katrukha, Ka Lou Yu, Roderick P. Tas, Sybren Portegies, Bastiaan J. Viergever, Esther de Graaff, Casper C. Hoogenraad, Eelco J. P. de Koning, Francoise Carlotti, Lukas C. Kapitein, Anna Akhmanova
Summary: Insulin secretion in pancreatic beta-cells is regulated by cortical complexes that are enriched at the sites of adhesion to the extracellular matrix. Non-neuronal proteins LL5 beta and KANK1 are also present at insulin secretion sites and are involved in organizing exocytotic machinery. The dynamics of ELKS, an essential component of secretory complexes, is driven by binding and unbinding to low-mobility scaffolds, which are stimulated by glucose treatment. This study provides insights into the spatial organization of glucose-stimulated insulin release.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemical Research Methods
Anna M. Kip, Juan Manuel Valverde, Maarten Altelaar, Ron M. A. Heeren, Inca H. R. Hundscheid, Cornelis H. C. Dejong, Steven W. M. Olde Damink, Benjamin Balluff, Kaatje Lenaerts
Summary: This study investigated the proteome and phosphoproteome changes in the human intestine during ischemia-reperfusion using LC-MS/MS and MSI techniques. The findings revealed alterations in proteins related to intestinal absorption, innate immunity, and extracellular matrix organization, as well as the activity of MAPK and CDK families during IR. The study highlights the importance of complementary use of different MS methodologies in understanding molecular changes during IR.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Biochemical Research Methods
David Vargas-Diaz, Maarten Altelaar
Summary: A high-throughput method was developed for the automated enrichment of newly synthesized proteins (NSPs) using metabolic labeling. The method enables specific selection of NSPs and enhances selectivity by chemical cleavage. It allows for digestion and mass spectrometry analysis of the enriched proteins.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Apoorva Sarode, Yuchen Fan, Amy E. Byrnes, Michal Hammel, Greg L. Hura, Yige Fu, Ponien Kou, Chloe Hu, Flora Hinz, Jasmine Roberts, Stefan G. Koenig, Karthik Nagapudi, Casper C. Hoogenraad, Tao Chen, Dennis Leung, Chun-Wan Yen
Summary: Lipid nanoparticles (LNPs) have gained attention in nucleic acid delivery field due to the success of mRNA COVID-19 vaccines. PEGylated lipids (PEG-lipids) as one of the constituent lipids on LNP surfaces play a crucial role in defining LNP properties. Research suggests that tuning PEG-lipid parameters can modulate LNP performance. To fully understand LNP behavior, a high-throughput screening (HTS) workflow was developed to prepare, characterize, and assess LNPs loaded with therapeutic antisense oligonucleotide (ASO).
NANOSCALE ADVANCES
(2022)
Article
Biochemistry & Molecular Biology
Elena Tortosa, Arundhati Sengupta Ghosh, Qingling Li, Weng Ruh Wong, Trent Hinkle, Wendy Sandoval, Christopher M. Rose, Casper C. Hoogenraad
Summary: The phosphorylation and membrane localization of DLK, a component of MAPK, is crucial for its activation during neuronal stress responses. The recruitment of DLK to specific vesicles upon stress induces kinase activation, which is essential for neuronal survival and degeneration.
Article
Biochemistry & Molecular Biology
Victoria G. Castiglioni, Joao J. Ramalho, Jason R. Kroll, Riccardo Stucchi, Hanna van Beuzekom, Ruben Schmidt, Maarten Altelaar, Mike Boxem
Summary: This study investigates the presence and function of PALS1 and PATJ orthologs in C. elegans. The results show that MAGU-2 interacts with all Crumbs proteins and localizes to the apical membrane domain of intestinal epithelial cells. Deletion of magu-2 does not result in epithelial polarity defects similar to crumbs mutants. MPZ-1 is identified as a candidate ortholog of PATJ but its expression is not widely observed in epithelial tissues, suggesting it is not a core component of the C. elegans Crumbs complex. Over-expression of Crumbs proteins EAT-20 or CRB-3 leads to apical membrane expansion in the intestine.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Cell Biology
Anna Bodzeta, Florian Berger, Harold D. MacGillavry
Summary: This study reveals the novel molecular mechanisms that control the nanoscale distribution and mobility of presynaptic metabotropic glutamate receptors (mGluRs) in hippocampal neurons. The high-affinity group II receptor mGluR2 is diffusely distributed along the axon and highly mobile, while the low-affinity group III receptor mGluR7 is stably anchored at the active zone. Computational modeling shows that this nanoscale arrangement directly impacts their ability to modulate neurotransmitter release.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Multidisciplinary Sciences
Georgi Apriamashvili, David W. Vredevoogd, Oscar Krijgsman, Onno B. Bleijerveld, Maarten A. Ligtenberg, Beaunelle de Bruijn, Julia Boshuizen, Joleen J. H. Traets, Daniela D'Empaire Altimari, Alex van Vliet, Chun-Pu Lin, Nils L. Visser, James D. Londino, Rebekah Sanchez-Hodge, Leah E. Oswalt, Selin Altinok, Jonathan C. Schisler, Maarten Altelaar, Daniel S. Peeper
Summary: This study identifies STUB1 as a critical regulator of the IFN gamma receptor (IFN gamma-R1), which affects the sensitivity of tumor cells to cytotoxic T cells. The researchers also find that STUB1 expression is inversely correlated with the IFN gamma response in immune checkpoint blockade (ICB) treated patients.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Stine Kjaer Morthorst, Camilla Nielsen, Pietro Farinelli, Zeinab Anvarian, Christina Birgitte R. Rasmussen, Andrea Serra-Marques, Ilya Grigoriev, Maarten Altelaar, Nicoline Furstenberg, Alexander Ludwig, Anna Akhmanova, Soren Tvorup Christensen, Lotte Bang Pedersen
Summary: A new interactor of KIF13B, Ap80, has been identified, which promotes the binding of PALS1 to KIF13B and regulates ciliary length, composition and signaling.
JOURNAL OF CELL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Susanne G. van der Grein, Kyra A. Y. Defourny, Huib H. Rabouw, Soenita S. Goerdayal, Martijn J. C. van Herwijnen, Richard W. Wubbolts, Maarten Altelaar, Frank J. M. van Kuppeveld, Esther N. M. Nolte-'t Hoen
Summary: This article investigates the role of the Leader protein in the non-lytic release of encephalomyocarditis virus (EMCV) through extracellular vesicles. The study reveals that the Leader protein promotes the release of virus particles enclosed in extracellular vesicles, and this process may involve secretory autophagy.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Liu He, Lotte van Beem, Berend Snel, Casper C. Hoogenraad, Martin Harterink
Summary: The neuronal microtubule cytoskeleton is crucial for establishing the polarity of axons and dendrites. In this study using Caenorhabditis elegans as a model, the roles of two microtubule minus-end related proteins, CAMSAP and NINEIN, in microtubule organization in dendrites were characterized. The results showed that CAMSAP and NINEIN function in parallel to mediate the correct orientation of microtubules in dendrites. RAB-11-positive vesicles were found to nucleate microtubules and act as a microtubule organizing center (MTOC) during dendrite outgrowth. CAMSAP and NINEIN were both important for localizing MTOC vesicles to the growing dendrite tip and organizing microtubules minus-end out.
Article
Chemistry, Analytical
Fujia Wang, Tim Veth, Marije Kuipers, Maarten Altelaar, Kelly E. Stecker
Summary: A successful mass spectrometry-based phosphoproteomics analysis relies on effective sample preparation strategies. The performance of the S-Trap protocol for phosphoproteomics studies is unclear, and the addition of phosphoric acid (PA) in the existing protocol is detrimental to downstream phosphopeptide enrichment. This study systematically evaluates the performance of the S-Trap digestion for proteomics and phosphoproteomics, and demonstrates that an optimized S-Trap approach, with trifluoroacetic acid substituted for PA, is a simple and effective method for phosphoproteomics sample preparation.
ANALYTICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Amelie Freal, Nora Jamann, Jolijn Ten Bos, Jacqueline Jansen, Naomi Petersen, Thijmen Ligthart, Casper C. Hoogenraad, Maarten H. P. Kole
Summary: This study reveals the molecular mechanisms underlying the plasticity of the axon initial segment (AIS) in response to changes in network activity, showing that the activation of N-methyl-D-aspartate receptors leads to internalization of sodium channels and an increase in action potential threshold.
Article
Cell Biology
Donna O. Debets, Kelly E. Stecker, Anastasia Piskopou, Marte C. Liefaard, Jelle Wesseling, Gabe S. Sonke, Esther H. Lips, Maarten Altelaar
Summary: This study performs (phospho)proteomics analysis of pre-treatment HER2+ needle biopsies of early-stage invasive breast cancer to identify molecular signatures predictive of treatment response. The study finds that accurate quantification of the estrogen receptor (ER) and HER2 biomarkers, along with the assessment of associated biological features, can improve treatment outcome prediction. Additionally, the study identifies cellular mechanisms that potentially precondition tumors to resist therapy.
CELL REPORTS MEDICINE
(2023)