Article
Biochemistry & Molecular Biology
Miranda Mele, Pasqualino De Luca, Ana Rita Santos, Marta Vieira, Ivan L. Salazar, Paulo S. Pinheiro, Carlos B. Duarte
Summary: This study investigated the regulation of the synaptic protein GRASP1 by ubiquitin-dependent mechanisms, revealing an impact on the surface distribution and activity of AMPA receptors. Ubiquitination was found to decrease dendritic levels of GRASP1 and surface expression of GluA1 subunits, leading to a reduction in mEPSC amplitudes, effects that were partially reversed by cotransfection with GRASP1.
Article
Multidisciplinary Sciences
Domenico Azarnia Tehran, Gaga Kochlamazashvili, Niccolo P. Pampaloni, Silvia Sposini, Jasmeet Kaur Shergill, Martin Lehmann, Natalya Pashkova, Claudia Schmidt, Delia Loewe, Hanna Napieczynska, Arnd Heuser, Andrew J. R. Plested, David Perrais, Robert C. Piper, Volker Haucke, Tanja Maritzen
Summary: This study reveals that the Alzheimer's disease risk factor CALM controls the surface levels of CP-AMPARs through endocytosis, and this regulation reciprocally modulates LTP and LTD in vivo to influence learning.
Editorial Material
Cell Biology
Yalan Wang, Hongyan Wang, Chenji Wang
Summary: In neuronal ceroid lipofuscinoses (NCLs), mutations in the KCTD7 gene lead to lysosomal dysfunction and macroautophagic/autophagic defects, resulting in the accumulation of lysosomal storage deposits. Our study demonstrates that KCTD7 is a key player in maintaining lysosomal and autophagic homeostasis, and it is biochemically linked with CLN5, another NCL causative gene, in a common neurodegenerative pathway.
Article
Immunology
Roberto R. Ricardo-Gonzalez, Maya E. Kotas, Claire E. O'Leary, Katelyn Singh, William Damsky, Chang Liao, Elizabeth Arouge, Iliana Tenvooren, Diana M. Marquez, Andrew W. Schroeder, Jarish N. Cohen, Marlys S. Fassett, Jinwoo Lee, Scott G. Daniel, Kyle Bittinger, Roberto Efrain Diaz, James S. Fraser, Niwa Ali, K. Mark Ansel, Matthew H. Spitzer, Hong-Erh Liang, Richard M. Locksley
Summary: This study reveals that the control of Demodex mite colonization in hair follicles in mice depends on group 2 innate lymphoid cells (ILC2s), interleukin-13 (IL-13), and its receptor, IL-4Ra-IL-13Ra1. ILC2s produce IL-13 which inhibits the proliferation of hair follicles and epithelial cells, preventing excessive growth caused by Demodex infestation. Human patients with rhinophymatous acne rosacea, associated with Demodex, also show increased follicular inflammation and decreased type 2 cytokines, similar to the findings in mice.
Article
Geriatrics & Gerontology
Xiangkun Meng, Zhe Huang, Aiko Inoue, Hailong Wang, Ying Wan, Xueling Yue, Shengnan Xu, Xueying Jin, Guo-Ping Shi, Masafumi Kuzuya, Xian Wu Cheng
Summary: This study suggests that cathepsin K (CTSK) plays a significant role in muscle wasting in cancer-related cachexia by mediating the ubiquitination of insulin receptor substrate 1 (IRS1).
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Multidisciplinary Sciences
Austin M. Ramsey, Ai-Hui Tang, Tara A. LeGates, Xu-Zhuo Gou, Beatrice E. Carbone, Scott M. Thompson, Thomas Biederer, Thomas A. Blanpied
Summary: Recent evidence suggests that nano-organization of proteins within synapses may control the strength of communication between neurons in the brain. Targeting LRRTM2, a key transsynaptic adhesion molecule, and disrupting its extracellular domain quickly led to nanoscale declustering of AMPARs, resulting in significant deficits in evoked postsynaptic receptor activation but not spontaneous activation. This indicates that adhesion molecules may acutely position receptors to dynamically control synaptic strength.
Article
Biochemistry & Molecular Biology
E. Anne Martin, Jennifer Carlisle Michel, Jane S. Kissinger, Fabio A. Echeverry, Ya-Ping Lin, John O'Brien, Alberto E. Pereda, Adam C. Miller
Summary: The subcellular positioning and molecular compositions of synapses are crucial for neural circuits. This study investigates the localization of the autism- and epilepsy-associated gene Neurobeachin, the Connexins, and the electrical synapse scaffold ZO1. It is found that Neurobeachin localizes to the electrical synapse independently, and its presence is necessary for the localization of ZO1 and Connexins. This research provides new insights into the molecular complexity and mechanisms of electrical synapse formation.
Article
Oncology
Yang Wang, Wen-Yi Gao, Li-Li Wang, Ruo-Lei Wang, Zhi-Xia Yang, Fu-Qiang Luo, Yu-Hao He, Zi-Bin Wang, Fu-Qiang Wang, Qing-Yuan Sun, Jing Li, Dong Zhang
Summary: This study revealed that knockout of the FBXW24 gene in female mice significantly affected fertility, follicle reserve, oocyte quality, meiotic prophase progression of female germ cells, and oocyte meiosis primarily by regulating the stability of SYCP3, ultimately leading to oocyte death and infertility.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Beibei Fu, Xiaoyuan Lin, Shun Tan, Rui Zhang, Weiwei Xue, Haiwei Zhang, Shanfu Zhang, Qingting Zhao, Yu Wang, Kelly Feldman, Lei Shi, Shaolin Zhang, Weiqi Nian, Krishna Chaitanya Pavani, Zhifeng Li, Xingsheng Wang, Haibo Wu
Summary: The research reveals that the miR-342-3p/SOCS6 axis plays a crucial role in regulating anti-Mtb immunity and the balance between cell apoptosis and necrosis during Mtb infection, providing new insights for developing host-directed therapies targeting these pathways.
Article
Multidisciplinary Sciences
Stavroula Bitsi, Liliane El Eid, Yusman Manchanda, Affiong I. Oqua, Nimco Mohamed, Ben Hansen, Kinga Suba, Guy A. Rutter, Victoria Salem, Ben Jones, Alejandra Tomas
Summary: This study reveals the important role of GLP-1R in the treatment of type 2 diabetes, and the rapid desensitization of stimulated GLP-1Rs by beta-arrestins. By studying KO mice, it was found that they had weaker responses to GLP-1R agonists, but showed improvement 6 hours after agonist injection. This study unveils fundamental aspects of GLP-1R response regulation with direct application to the rational design of GLP-1R-targeting therapeutics.
Review
Cell Biology
Zehui Lei, Jing Wang, Lingqiang Zhang, Cui Hua Liu
Summary: Membrane trafficking relies on the regulation of small GTPases, which can be modulated through post-translational modifications such as ubiquitination. Dysregulation of small GTPase ubiquitination may lead to various human diseases, highlighting the importance of understanding the molecular mechanisms involved.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
You-Sheng Lin, Yung-Chi Chang, Tai-Ling Chao, Ya-Min Tsai, Shu-Jhen Jhuang, Yu-Hsin Ho, Ting-Yu Lai, Yi-Ling Liu, Chiung-Ya Chen, Ching-Yen Tsai, Yi-Ping Hsueh, Sui-Yuan Chang, Tsung-Hsien Chuang, Chih-Yuan Lee, Li-Chung Hsu
Summary: The termination mechanism of TLR3 signaling is crucial for antiviral immunity. The E3 ubiquitin ligase ZNRF1 regulates TLR3 sorting into lysosomes, leading to the termination of TLR3 signaling and interferon production. ZNRF1-deficient mice and cells are resistant to specific viral infections but more susceptible to bacterial superinfection due to lung barrier damage.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Oncology
Masakazu Goto, Yukiko Shibahara, Cristina Baciu, Frances Allison, Jonathan C. Yeung, Gail E. Darling, Mingyao Liu
Summary: This study found that high expression of CXCR7 is associated with poor prognosis in patients with esophageal adenocarcinoma, and the combination of high expression of CXCR7 and CXCL12 has a stronger association with prognosis. Additionally, high expression of both CXCR7 and CXCL12 was identified as an independent prognostic factor for overall and disease-free survival in patients with esophageal adenocarcinoma. Further research with larger sample sizes is warranted to explore the potential of this biomarker.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Article
Cell Biology
Narumi Suzuki, Yoshikazu Johmura, Teh-Wei Wang, Toshiro Migita, Wenwen Wu, Rei Noguchi, Kiyoshi Yamaguchi, Yoichi Furukawa, Shuhei Nakamura, Ichiro Miyoshi, Tamotsu Yoshimori, Tomohiko Ohta, Makoto Nakanishi
Summary: The study demonstrates that TP53 upregulates basal autophagy through the FBXO22-TFEB axis, governing the hormetic effect in chemotherapy.
Article
Multidisciplinary Sciences
Tatenda Mahlokozera, Bhuvic Patel, Hao Chen, Patrick Desouza, Xuan Qu, Diane D. Mao, Daniel Hafez, Wei Yang, Rukayat Taiwo, Mounica Paturu, Afshin Salehi, Amit D. Gujar, Gavin P. Dunn, Nima Mosammaparast, Allegra A. Petti, Hiroko Yano, Albert H. Kim
Summary: The research reveals that the E3 ubiquitin ligase TRIM26 promotes SOX2 stability in a unique manner, consequently enhancing the tumorigenicity and tumor-forming ability of GSCs.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Rob Hill, Meritxell Canals
Summary: Morphine and other opioids are widely used for pain treatment, but their side effects limit their use. Developing opioids with fewer side effects is a major research focus, but translating promising candidates from the lab to the clinic remains challenging.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Gastroenterology & Hepatology
Jesse J. DiCello, Simona E. Carbone, Ayame Saito, Vi Pham, Agata Szymaszkiewicz, Arisbel B. Gondin, Sadia Alvi, Kiliana Marique, Priyank Shenoy, Nicholas A. Veldhuis, Jakub Fichna, Meritxell Canals, Arthur Christopoulos, Celine Valant, Daniel P. Poole
Summary: This study investigates the modulation of delta opioid receptor in the enteric nervous system using allosteric modulators, demonstrating the potential of positive allosteric modulation as a pharmacological approach to enhance opioid receptor signaling and suppress colonic motility. The findings suggest that allosteric modulation of opioid receptor signaling could be a therapeutic strategy for conditions such as irritable bowel syndrome.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Rob Hill, Andrew C. Kruegel, Jonathan A. Javitch, J. Robert Lane, Meritxell Canals
Summary: The study found differential effects of Mitragynine and its metabolite, 7-OH Mitragynine, on mouse respiration and anti-nociception. Mitragynine showed a ceiling effect on respiratory depression, while 7-OH Mitragynine had dose-dependent effects. Inhibition of CYP3A reduced the respiratory depressant effects and anti-nociception induced by Mitragynine, but had no effect on the effects of 7-OH Mitragynine. These findings suggest that metabolic saturation may contribute to the improved safety profile of Mitragynine.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Cell Biology
Maria P. Kotini, Miesje M. van der Stoel, Jianmin Yin, Mitchell K. Han, Bettina Kirchmaier, Johan de Rooij, Markus Affolter, Stephan Huveneers, Heinz-Georg Belting
Summary: Blood vessel morphogenesis is driven by coordinated endothelial cell behaviors. Active remodeling of cell-cell junctions promotes cellular plasticity while preserving vascular integrity. Lumen expansion in angiogenic sprouts is accompanied by the formation of transient finger-shaped junctions. Blood pressure positively regulates the formation of junctional fingers, while flow inhibition prevents their formation. Mechanotransduction protein vinculin is recruited to junctional fingers, and its genetic deletion prevents finger formation. Endothelial cells employ force-dependent junctional remodeling to counteract external forces and maintain vascular integrity during sprouting angiogenesis.
Article
Biochemistry & Molecular Biology
Hendrik J. Brink, Rick Riemens, Stephanie Thee, Berend Beishuizen, Daniel da Costa Pereira, Maikel Wijtmans, Iwan de Esch, Martine J. Smit, Albertus H. de Boer
Summary: In this study, a fragment-based drug screening approach was used to identify a PPI stabilizer targeting 14-3-3. The stabilizer was found to cooperatively stabilize 14-3-3 and enhance its binding to client proteins. This finding provides a tool compound for investigating the interactions between 14-3-3 and client proteins.
Article
Multidisciplinary Sciences
Andrew B. Kleist, Shawn Jenjak, Andrija Sente, Lauren J. Laskowski, Martyna Szpakowska, Maggie M. Calkins, Emilie Anderson, Lisa M. McNally, Raimond Heukers, Vladimir Bobkov, Francis C. Peterson, Monica A. Thomas, Andy Chevigne, Martine J. Smit, John D. McCorvy, M. Madan Babu, Brian F. Volkman
Summary: NMR experiments on ACKR3 revealed that the recruitment of beta-arrestins is associated with conformational exchange at key regions of the receptor, and identified an allosteric hub in the core receptor that coordinates transitions among different conformational states, guiding beta-arrestin recruitment.
Article
Engineering, Biomedical
Bin Li, Arzu Colak, Johanna Blass, Mitchell Han, Jingnan Zhang, Yijun Zheng, Qiyang Jiang, Roland Bennewitz, Aranzazu del Campo
Summary: Studying cells' response to the macroscopic and nanoscale properties of biomaterials requires model systems with different length scales. IPN design can offer insights into cell adhesion and spreading behaviors, presenting different mechanical cues at the molecular scale but similar properties at the macroscopic length scale. Cells adhered to the IPN guest network with lower molecular stiffness exhibited distinct characteristics compared to those attached to the single network.
MATERIALS TODAY BIO
(2022)
Article
Education & Educational Research
Mirella Jongsma, Danny J. Scholten, Jacqueline E. van Muijlwijk-Koezen, Martijn Meeter
Summary: This paper conducts a meta-analysis comparing the effectiveness of online and offline peer feedback in higher education, finding that online peer feedback is more effective. Moreover, online peer feedback is more effective in assessing competence and students generally have a positive attitude towards it, although there are also some downsides.
JOURNAL OF EDUCATIONAL COMPUTING RESEARCH
(2023)
Letter
Biochemistry & Molecular Biology
Hendrik J. Brink, Jeffrey R. van Senten, Ingrid J. De Vries-van Leeuwen, Daniel da Costa Pereira, Sander R. Piersma, Connie R. Jimenez, Federica Centorrino, Christian Ottmann, Marco Siderius, Martine J. Smit, Albertus H. de Boer
Summary: CIP2A is an oncoprotein that is overexpressed in many types of cancer, and it stabilizes other oncoproteins to promote tumor development. This study discovered that the penultimate residue Ser904 in the C-terminus of CIP2A can be phosphorylated, allowing it to bind with the regulatory protein 14-3-3. Additionally, a protein-protein interaction stabilizer called FC-A can enhance the phosphorylation of Ser904 and increase the association between CIP2A and 14-3-3. This provides a new potential method to modulate the activity of CIP2A.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biology
Matyas A. Bittenbinder, Nick D. Bergkamp, Julien Slagboom, Jan Paul M. Bebelman, Nicholas R. Casewell, Marco H. Siderius, Martine J. Smit, Jeroen Kool, Freek J. Vonk
Summary: Snakebite envenoming is a significant public health concern with high mortality rates. Snake venoms can have various harmful effects on the body, including tissue damage. This study presents a workflow using fluorescently labeled ECM components to investigate the degradation of ECM caused by snake venom. This approach provides valuable insights into the mechanisms of proteolytic venom components and could aid in the development of effective snakebite treatments.
Article
Pharmacology & Pharmacy
Rob Hill, Julie Sanchez, Laura Lemel, Mirjana Antonijevic, Yselkla Hosking, Shailesh N. Mistry, Andrew C. Kruegel, Jonathan A. Javitch, J. Robert Lane, Meritxell Canals
Summary: This study evaluated the effects of three novel opioids on respiratory depression and analgesia, and compared these measurements with their in vitro efficacy. The results showed that these opioids can induce respiratory depression and analgesia at certain doses, but there are differences in potency and duration of effect among the novel opioids.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nick D. Bergkamp, Jeffrey R. van Senten, Hendrik J. Brink, Maarten P. Bebelman, Jelle van den Bor, Tugce S. Cobanoglu, Kasper Dinkla, Johannes Koester, Gunnar Klau, Marco Siderius, Martine J. Smit
Summary: The G-protein coupled receptor US28 encoded by human cytomegalovirus (HCMV) is associated with accelerated progression of glioblastomas. In this study, it was found that US28 enhances signaling mediated by sphingosine-1-phosphate (S1P), promoting glioblastoma cell proliferation and survival. The study also uncovers the roles of S1P and CIP2A in US28-mediated exacerbation of glioblastoma.
Article
Multidisciplinary Sciences
Maarten P. Bebelman, Irfan M. Setiawan, Nick D. Bergkamp, Jeffrey R. van Senten, Caitrin Crudden, Jan Paul M. Bebelman, Frederik J. Verweij, Guillaume van Niel, Marco Siderius, D. Michiel Pegtel, Martine J. Smit
Summary: The HCMV-encoded chemokine receptor US28 plays a role in various aspects of the viral life cycle and immune evasion by scavenging chemokines from HCMV-infected cells. It localizes to late endosomal compartments called multivesicular bodies (MVBs) and can be secreted on exosomes through fusion with the plasma membrane. The exosomal release of US28 contributes to chemokine scavenging and immune evasion by HCMV.
Article
Biochemical Research Methods
Jelle van den Bor, Nick D. Bergkamp, Stephanie M. Anbuhl, Francoise Dekker, Dehan Comez, Claudia V. Perez Almeria, Reggie Bosma, Carl W. White, Laura E. Kilpatrick, Stephen J. Hill, Marco Siderius, Martine J. Smit, Raimond Heukers
Summary: The use of nanobodies and NanoBRET methods allows for real-time monitoring of nanobody-receptor binding, predicting the therapeutic potential of ligands targeting disease-associated membrane proteins, which is significant for drug research.
CELL REPORTS METHODS
(2023)
Letter
Oncology
Gamal A. Wakileh, Philipp Bierholz, Mara Kotthoff, Margaretha A. Skowron, Felix Bremmer, Alexa Stephan, Stephanie M. Anbuhl, Raimond Heukers, Martine J. Smit, Philipp Stroebel, Daniel Nettersheim
Summary: This study identified a nanobody-drug-conjugate targeting CXCR4 as a potential therapeutic option for GCT. Furthermore, this study shed light on the functional role of the CXCR4 / CXCR7 / CXCL12-signaling cascade in GCT, demonstrating an important influence on proliferation and migration.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2023)