Article
Multidisciplinary Sciences
Hongbin Li, Vishaal Rajani, Lu Han, Danielle Chung, James E. Cooke, Ameet S. Sengar, Michael W. Salter
Summary: NMDA receptors (NMDARs) are a principal subtype of excitatory neurotransmitter receptor, composed of two GluN1 and two GluN2 subunits. Alternative splicing of GluN1 can affect the signaling of glycine, which is crucial for the nonionotropic signaling by NMDARs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Endocrinology & Metabolism
Alexis Z. L. Shih, Yi-Chun Chen, Thilo Speckmann, Esben Sondergaard, Annette Schuermann, C. Bruce Verchere, Thomas E. Willnow
Summary: This study reveals that the sorting-related receptor SORLA plays a protective role in pancreatic islets by preventing amyloid deposition and associated cell death caused by islet amyloid polypeptide. SORLA mediates the endocytic uptake of proIAPP, reducing the accumulation of amyloid peptides in islets.
MOLECULAR METABOLISM
(2022)
Article
Multidisciplinary Sciences
Tebbe de Vries, William Martelly, Sebastien Campagne, Kevin Sabath, Chris P. Sarnowski, Jason Wong, Alexander Leitner, Stefanie Jonas, Shalini Sharma, Frederic H. -T. Allain
Summary: This study determined the 3D structure of the complex between SF3A1-UBL and U1-SL4 RNA and revealed the sequence-specific recognition of U1-SL4 by SF3A1-UBL. The results expand our understanding of RNA binding domains and demonstrate the specific binding capacity of RGG/RG motifs to RNA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Sara R. Roig, Laura Sole, Silvia Cassinelli, Magali Colomer-Molera, Daniel Sastre, Clara Serrano-Novillo, Antonio Serrano-Albarras, M. Pilar Lillo, Michael M. Tamkun, Antonio Felipe
Summary: The voltage-dependent potassium channel Kv1.3 is crucial for immune response, with regulatory subunit KCNE4 tightly modulating its function and membrane localization. The interaction between KCNE4 and CaM controls KCNE4's regulation of Kv1.3 and its cellular trafficking mechanism.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Xiaokang Zhang, Chao Wang, Linlu Qi, Shiwei Wang, Yitong Chen, Zhiwei Kong, Saijie Li, Xin Zhang, Zhengguang Zhang, Junfeng Liu, Dongli Wang
Summary: Clathrin-mediated endocytosis (CME) is crucial for physiological processes in eukaryotic cells. In fungi, the Pan1/End3/Sla1 complex regulates the transition between early and late stages of CME. This study uncovers the detailed interaction mechanism between MoEnd3 and MoSla1 in the pathogenic fungus Magnaporthe oryzae, revealing the synergistic effect of EH domains in improving affinity and specificity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Delong Zhou, Yvan Tran, Sherif Abou Elela, Michelle S. Scott
Summary: SAPFIR is a predictor of protein features associated with alternative splicing events, allowing for rapid identification of functional alternative splicing events and analysis of proteins generated from diverse genes, providing guidance on the impact on cellular functions.
BMC BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Tingting Zhou, Youlei He, Xianqi Zeng, Binhua Cai, Shenchun Qu, Sanhong Wang
Summary: In this study, RNA-Seq analysis was performed to investigate the alternative splicing (AS) divergence in two apple cultivars infected with Alternaria alternata AP. The results showed that apple triggers specific AS in response to Alternaria alternata AP infection, and differentially spliced genes (DSGs) are significantly enriched in multiple levels of gene expression regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Vinh Vu, Taylor Light, Brendan Sullivan, Diana Greiner, Kalina Hristova, Deborah Leckband
Summary: The study presents a new mechanism of E-cadherin oligomerization and demonstrates that binding of p120ctn protein is essential for constitutive E-cadherin dimerization. This finding challenges the traditional model of cadherin assembly at cell surfaces and sheds light on the core building blocks of cadherin-mediated intercellular adhesions.
Article
Multidisciplinary Sciences
Richard M. Hooy, Yuichiro Iwamoto, Dan A. Tudorica, Xuefeng Ren, James H. Hurley
Summary: Adaptor protein (AP) complexes play important roles in membrane trafficking and immune evasion in HIV-1 infection. The self-assembly of AP-1:Arf1 coats on tubulated membranes provides a structural basis for the formation of clathrin vesicles and the sequestration of MHC-I.
Article
Plant Sciences
Lu Zhang, Yuanming Liu, Qiaohui Wang, Chao Wang, Shikai Lv, Yanzhen Wang, Jianfeng Wang, Yajuan Wang, Jing Yuan, Hong Zhang, Zhensheng Kang, Wanquan Ji
Summary: This study reveals the mechanism of alternative splicing and protein interaction of the wheat R gene TaYRG1, which enhances resistance to Puccinia striiformis f. sp. tritici and triggers cell death. It also identifies the interaction between TaYRG1 and a dynamin-related protein, suggesting a potential role in membrane trafficking and endocytosis pathway.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Biotechnology & Applied Microbiology
A. Gallo, D. Dolfini, A. Bernardini, N. Gnesutta, R. Mantovani
Summary: NF-YA, the regulatory subunit of the trimeric CCAAT-binding transcription factor NF-Y, has multiple alternative spliced isoforms, and NF-YAx and NF-YAg are enriched in Aves and play a major role in early chicken embryo development. In addition, the absence of exon-5 in NF-YAg leads to a global reduction of beta-stranded elements, while removal of the disordered exon-3 sequence has limited effects on TAD architecture.
Article
Genetics & Heredity
Carlos Alberto Gonzalez-Dominguez, Moises O. Fiesco-Roa, Samuel Gomez-Carmona, Anke Paula Ingrid Kleinert-Altamirano, Miao He, Earnest James Paul Daniel, Kimiyo M. Raymond, Melania Abreu-Gonzalez, Sandra Manrique-Hernandez, Ana Gonzalez-Jaimes, Roberta Salinas-Marin, Carolina Molina-Garay, Karol Carrillo-Sanchez, Luis Leonardo Flores-Lagunes, Marco Jimenez-Olivares, Anallely Munoz-Rivas, Mario E. Cruz-Munoz, Matilde Ruiz-Garcia, Hudson H. Freeze, Hector M. Mora-Montes, Carmen Alaez-Verson, Ivan Martinez-Duncker
Summary: This study reports a Mexican mestizo patient with a multi-systemic syndrome involving neurological issues and a type I serum transferrin profile. Clinical exome sequencing identified complex alleles in the ALG1 gene, leading to the diagnosis of ALG1-CDG. The discovery of a previously uncharacterized variant in conjunction with a known pathogenic variant defines the pathogenic protein effect in this patient.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Huijun Yang, Weijing Liu, Shen Song, Lina Bai, Yu Nie, Yongping Bai, Guogang Zhang
Summary: This study identified a complex gene network and hub genes controlling heart maturation through proteomic and transcriptomic analysis. Functional and pathway analysis revealed that these genes mainly contribute to heart maturation by regulating mRNA processing and energy metabolism. In addition, it was found that some important sarcomere and energy-associated genes undergo different alternative splicing events.
Article
Oncology
Qi Wen Chen, Qian Qian Cai, Ying Yang, Shu Dong, Yuan Yuan Liu, Zhong Yi Chen, Chun Lan Kang, Bing Qi, Yi Wei Dong, Wei Wu, Li Ping Zhuang, Ye Hua Shen, Zhi Qiang Meng, Xing Zhong Wu
Summary: This study reveals the important role and mechanism of long non-coding RNA BC in promoting tumor metastasis and influencing clinical prognosis of lung adenocarcinoma (LUAD). BC promotes growth, invasion, metastasis, and resistance to EGFR-targeted therapies in lung cancer by forming a splicing complex with nucleolin and hnRNPK. High expression of BC is associated with clinical progress and poor survival in LUAD.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Yawen Bu, Qingyuan Teng, Delan Feng, Rong Liang, Haoran Wang, Xuehui Zhang, Xiao Li, Wenfeng Jia, Jia Xue, Ye Zhao, Guozhong Zhang
Summary: This study reveals the importance of the YLMY motif in the intracellular trafficking of Newcastle disease virus (NDV) F protein. The YLMY motif regulates the transport of F protein to the cell surface through host adaptor protein (AP) complexes and affects viral titer. Mutations in the YLMY motif also alter the interaction between F protein and AAK1 and GAK kinases. These findings contribute to a better understanding of virus-host determinants and can be utilized for the development of antiviral therapies.
Article
Psychiatry
Ditte Olsen, Niels Wellner, Mathias Kaas, Inge E. M. de Jong, Florence Sotty, Michael Didriksen, Simon Glerup, Anders Nykjaer
Summary: Attention deficit hyperactivity disorder (ADHD) is the most frequently diagnosed neurodevelopmental disorder worldwide, and Sorcs2(-/-) mice can replicate symptoms reminiscent of ADHD. Research shows that loss of the SorCS2 gene affects dopaminergic circuit function and behavioral responses to the environment.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Diana Hudecz, Sara Bjork Sigurdardottir, Sarah Christine Christensen, Casper Hempel, Andrew J. Urquhart, Thomas Lars Andresen, Morten S. Nielsen
Summary: The blood-brain barrier presents a challenge for brain disease therapies, but vesicular transport can be used as a strategy for delivery. Two peptides are capable of transcytosing across murine brain endothelial cells via vesicular transport.
Article
Neurosciences
Giulia Monti, Mads Kjolby, Anne Mette G. Jensen, Mariet Allen, Juliane Reiche, Peter L. Moller, Raquel Comaposada-Baro, Bartlomiej E. Zolkowski, Carmen Vieira, Margarita Melnikova Jorgensen, Ida E. Holm, Paul N. Valdmanis, Niels Wellner, Christian B. Vaegter, Sarah J. Lincoln, Anders Nykjaer, Nilufer Ertekin-Taner, Jessica E. Young, Mette Nyegaard, Olav M. Andersen
Summary: This study identified a novel exon in SORL1 transcript encoding a truncated protein, which showed significantly reduced levels in the cerebellum of AD patients. These findings suggest potential synaptic functions for SORL1-38b in the brain.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Cell Biology
Marcel Klein, Abuzar Kaleem, Sandra Oetjen, Daniela Wuenkhaus, Lars Binkle, Sandra Schilling, Milena Gjorgjieva, Ralf Scholz, Doris Gruber-Schoffnegger, Stephan Storch, Stefan Kins, Gerard Drewes, Sabine Hoffmeister-Ullerich, Dietmar Kuhl, Guido Hermey
Summary: The study suggests that PSENEN and CLN3 may play important roles in the autophagy-lysosome system in a gamma-secretase activity-independent manner, indicating common cytopathological processes underlying different neurodegenerative diseases. The findings reveal a potential link between these two proteins in regulating cellular functions related to neurodegeneration.
Article
Biochemistry & Molecular Biology
Andrea E. Toth, Hans C. Helms, Andras Harazin, Kasper B. Johnsen, Charlotte Goldeman, Annette Burkhart, Maj S. Thomsen, Paul J. Kempen, Adrian Klepe, Dora V. Lipka, Peter L. Moller, Thomas L. Andresen, Mette Nyegaard, Torben Moos, Birger Brodin, Morten S. Nielsen
Summary: Sortilin acts as a crucial regulatory protein for maintaining the tightness of the blood-brain barrier (BBB). Lack of sortilin results in BBB leakage, potentially due to alterations in signalling pathways, leading to compromised connections between brain endothelial cells.
Editorial Material
Cell Biology
Guido Hermey
NEURAL REGENERATION RESEARCH
(2022)
Article
Neurosciences
Lars Binkle, Marcel Klein, Uwe Borgmeyer, Dietmar Kuhl, Guido Hermey
Summary: SorLA is an important receptor involved in neuronal endosomal sorting, with the ability to interact with various ligands, including those related to Alzheimer's disease. It plays a crucial role in neuronal endosomal sorting mechanisms and may function as a multifunctional receptor with intracellular sorting capacities.
Article
Neurosciences
Parvez Alam, Mikkel R. Holst, Line Lauritsen, Janni Nielsen, Simone S. E. Nielsen, Poul Henning Jensen, Jonathan R. Brewer, Daniel E. Otzen, Morten S. Nielsen
Summary: In this study, the researchers investigated the uptake and transport mechanisms of alpha-synuclein monomers and oligomers across the blood-brain barrier (BBB). They found that both monomers and oligomers were internalized by brain endothelial cells, with a higher restriction of oligomeric transport. Additionally, they discovered that monomeric alpha-synuclein trafficked via carriers decorated with Rab7. Knockdown of Caveolin1, VPS35, and Rab7 affected the transcytosis of monomeric alpha-synuclein, suggesting a polarized regulation of its vesicular transport. These findings highlight the importance of Rab7 in the trafficking of monomeric alpha-synuclein across the BBB, suggesting it could be a potential target for therapeutic strategies against Parkinson's disease.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Article
Medicine, Research & Experimental
Anna Scotto Rosato, Einar K. Krogsaeter, Dawid Jaslan, Carla Abrahamian, Sandro Montefusco, Chiara Soldati, Barbara Spix, Maria Teresa Pizzo, Giuseppina Grieco, Julia Boeck, Amanda Wyatt, Daniela Wuenkhaus, Marcel Passon, Marc Stieglitz, Marco Keller, Guido Hermey, Sandra Markmann, Doris Gruber-Schoffnegger, Susan Cotman, Ludger Johannes, Dennis Crusius, Ulrich Boehm, Christian Wahl-Schott, Martin Biel, Franz Bracher, Elvira De Leonibus, Elena Polishchuk, Diego L. Medina, Dominik Paquet, Christian Grimm
Summary: This study found that TPC2 activation can improve cellular phenotypes associated with LSDs, including cholesterol or lipofuscin accumulation and abnormal vacuole formation. Validation in patient cells and mouse models suggests that TPC2 is a promising target for the treatment of different types of LSDs.
EMBO MOLECULAR MEDICINE
(2022)
Editorial Material
Cell Biology
Andrea E. Toth, Morten S. Nielsen
NEURAL REGENERATION RESEARCH
(2023)
Article
Neurosciences
Simone S. E. Nielsen, Mikkel R. Holst, Kristine Langthaler, Elisabeth Helena Bruun, Birger Brodin, Morten S. Nielsen
Summary: The mechanisms of transferrin receptor trafficking across brain capillary endothelial cells are not well understood but are important for maintaining brain iron homeostasis and developing drug delivery strategies. This study used expansion microscopy and immunofluorescence-based transport studies to investigate the distribution and sorting of transferrin receptor in these cells. The findings reveal different sorting mechanisms for transferrin receptor depending on the direction of trafficking, with the highest transcytosis capacity observed in the brain-to-blood direction. These results have implications for understanding brain iron homeostasis and optimizing drug delivery to the brain.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Biochemistry & Molecular Biology
Emily L. Relton, Nicolas J. Roth, Seda Yasa, Abuzar Kaleem, Guido Hermey, Christopher J. Minnis, Sara E. Mole, Tatyana Shelkovnikova, Stephane Lefrancois, Peter J. McCormick, Nicolas Locker
Summary: The assembly of membrane-less organelles called stress granules (SGs) is important for cells to respond and adapt to stress. SGs condense stalled mRNAs and proteins to modulate cellular activities and promote survival. Disassembly of SGs is crucial for cell viability, and mutations leading to persistent or aberrant SGs are associated with neurodegenerative diseases. In the case of CLN3 mutations, which cause juvenile neuronal ceroid lipofuscinosis, loss of CLN3 function disrupts SG dynamics and poses challenges for treating this childhood disease.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Neurosciences
Mikkel Roland Holst, Nienke Marije de Wit, Burak Ozguer, Andreas Brachner, Kathrine Hyldig, Antje Appelt-Menzel, Hannah Sleven, Zameel Cader, Helga Eveline de Vries, Winfried Neuhaus, Allan Jensen, Birger Brodin, Morten Schallburg Nielsen
Summary: This study presents an experimental setup to evaluate different receptors for targeted delivery of therapeutic antibodies at the blood-brain barrier. The findings suggest that transferrin receptor and sortilin are effective receptors for intracellular delivery of antibodies, while CD133 and podocalyxin are static and inefficient receptors for antibody delivery. Additionally, sortilin is proposed as a cargo receptor for delivering therapeutic antibodies to brain microvascular endothelium. The hiPSC-BECs can serve as a model system for studying receptor-mediated transcytosis drug delivery at the human blood-brain barrier in vitro.
FLUIDS AND BARRIERS OF THE CNS
(2023)