Article
Cell Biology
Hideyuki Nakashima, Keita Tsujimura, Koichiro Irie, Takuya Imamura, Cleber A. Trujillo, Masataka Ishizu, Masahiro Uesaka, Miao Pan, Hirofumi Noguchi, Kanako Okada, Kei Aoyagi, Tomoko Andoh-Noda, Hideyuki Okano, Alysson R. Muotri, Kinichi Nakashima
Summary: This study reveals the mechanism of MeCP2/miR-199a axis in regulating neural stem cell differentiation, further confirming the importance of BMP signaling in RTT brain development, and proposing the MeCP2/miR-199a/Smad1 axis as a potential therapeutic target for RTT.
Article
Biochemistry & Molecular Biology
Callista B. Harper, Eva-Maria Blumrich, Michael A. Cousin
Summary: The study highlights the crucial role of the cytoplasmic C terminus of synaptophysin (Syp) in facilitating the accurate retrieval of synaptobrevin-II (SybII) during synaptic vesicle endocytosis. Neurons lacking Syp show defects in SybII retrieval, emphasizing the importance of a conformational change within the Syp C terminus for proper binding and retrieval. Importantly, the study suggests that Syp's presynaptic role is specifically related to the control of SybII retrieval, without affecting the kinetics of synaptic vesicle endocytosis at physiological temperatures.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yan Zhao, Hui Shi, Ying Pan, Mohan Lyu, Zhixuan Yang, Xiaoxia Kou, Xing Wang Deng, Shangwei Zhong
Summary: A study found that Ca2+ signaling in photosynthetic plants controls the nuclear translocation of photoreceptor phyB during the transition from darkness to light. Red light stimulates cytosolic Ca2+ increases via phyB, which are sensed by Ca2+-binding protein kinases CPK6 and CPK12. Upon Ca2+ activation, CPK6/12 directly interact with and phosphorylate photo-activated phyB at Ser80/Ser106 to initiate phyB nuclear import. This research uncovers a biochemical regulatory loop in phyB phototransduction and provides a paradigm for connecting ubiquitous Ca2+ increases to specific responses in sensory stimulus processing.
Article
Plant Sciences
Loren Castaings, Carine Alcon, Thibault Kosuth, David Correia, Catherine Curie
Summary: NRAMP1 transporter mediates plant survival of manganese deficiency by controlling manganese entry into root cells. The phosphorylation of NRAMP1 triggers its endocytosis and membrane distribution, regulating plant tolerance to manganese toxicity. Interrupting NRAMP1 membrane cycling leads to increased manganese toxicity, challenging the belief that manganese is only marginally toxic to plants.
Article
Biology
Konrad Lang, Julian Milosavljevic, Helena Heinkele, Mengmeng Chen, Lea Gerstner, Dominik Spitz, Severine Kayser, Martin Helmstaedter, Gerd Walz, Michael Koettgen, Andrew Spracklen, John Poulton, Tobias Hermle
Summary: This study investigates the dynamics of the slit diaphragm multiprotein complex in podocyte-like nephrocytes of Drosophila. It reveals the regulatory role of endocytosis in the slit diaphragm and the maintenance of its filtration barrier function. Understanding the mechanisms of slit diaphragm maintenance is crucial for the development of novel therapies for proteinuric renal diseases.
Article
Multidisciplinary Sciences
Jin Ye, Guichang Zou, Ruichi Zhu, Chao Kong, Chenjian Miao, Mingjie Zhang, Jianchao Li, Wei Xiong, Chao Wang
Summary: GABARAP and GABARAPL1 stabilize GABA(A) receptors by directly binding to the γ 2 subunit, promoting receptor trafficking pathways, and modulating receptor localization at synapses.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Kai-Kai Lu, Ru-Feng Song, Jia-Xing Guo, Yu Zhang, Jia-Xin Zuo, Hui-Hui Chen, Cai-Yi Liao, Xiao-Yu Hu, Feng Ren, Ying-Tang Lu, Wen-Cheng Liu
Summary: The study found that CycC1;1 interacts with the transcription factor WRKY75 to inhibit the transcriptional activation of SOS1, thereby reducing SOS1 expression and decreasing salt stress tolerance in Arabidopsis under low salinity conditions. However, under high salinity conditions, increased expression of WRKY75 and decreased expression of CycC1;1 promote SOS1 transcription and enhance plant salt tolerance.
Article
Urology & Nephrology
Haijiao Zhang, Lin Lin, Jianping Liu, Lifeng Pan, Zhijie Lin, Mingjie Zhang, Jiong Zhang, Ying Cao, Jinwei Zhu, Rongguang Zhang
Summary: The slit diaphragm is a specialized adhesion junction that forms the final filtration barrier in the kidney. Key components at the slit diaphragm can spontaneously undergo phase separation, driving the formation of highly dense condensates and recruitment of adhesion molecules. Mutations in these components can lead to impaired formation of slit diaphragm condensates and enrichment of key proteins, ultimately impacting kidney function.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Cell Biology
Shikha T. Ramesh, Kolaparamba V. Navyasree, Sneha Sah, Anjitha B. Ashok, Nishada Qathoon, Suryasikha Mohanty, Rajeeb K. Swain, Perunthottathu K. Umasankar
Summary: This study uncovers the role of an uncharacterized kinase BMP2K in AP-2 phosphorylation, demonstrating that BMP2K interacts with AP-2 via its C-terminus, and this interaction is crucial for CCP localization and function. The decline of endogenous BMP2K levels upon AP-2 impairment suggests a stabilizing relationship, and functional inactivation of BMP2K in zebrafish embryos leads to gastrulation phenotypes similar to AP-2 loss-of-function, highlighting the physiological relevance of BMP2K in vertebrates.
Article
Cell Biology
Ada Nowosad, Justine Creff, Pauline Jeannot, Raphael Culerrier, Patrice Codogno, Stephane Manenti, Laurent Nguyen, Arnaud Besson
Summary: In response to glucose starvation, p27 promotes autophagy by facilitating autophagosome trafficking along microtubule tracks via maintaining elevated microtubule acetylation through an ATAT1-dependent mechanism.
CELL DEATH & DISEASE
(2021)
Article
Biology
Angel Loza-Valdes, Alexander E. Mayer, Toufic Kassouf, Jonathan Trujillo-Viera, Werner Schmitz, Filip Dziaczkowski, Michael Leitges, Andreas Schlosser, Grzegorz Sumara
Summary: Members of the protein kinase D (PKD) family play a key role in integrating hormonal and nutritional inputs to regulate cellular metabolism. Specifically, PKD3 has been shown to promote insulin sensitivity, suppress lipogenesis, and regulate cAMP-dependent PKA activity in response to glucagon and fasting in the liver. The identification of over 300 potential PKD3 targets suggests its involvement in various metabolic processes, including glucose and tyrosine metabolism through the regulation of key enzymes like phenylalanine hydroxylase (PAH).
LIFE SCIENCE ALLIANCE
(2021)
Article
Biochemical Research Methods
Yue Zhou, Hiroaki Sakurai
Summary: Evidence has shown that ligand-bound activated EGFR dimers undergo endocytosis through clathrin-mediated and clathrin-independent processes, while non-ligand EGFR monomers are endocytosed through a non-canonical clathrin-mediated process triggered by cellular stress. We propose a dual-mode endocytosis model that integrates ligand-induced and stress-induced events. This new model challenges our established understanding of EGFR trafficking and has implications for anti-EGFR therapy.
JOURNAL OF PROTEOMICS
(2022)
Article
Biology
Xiuke Ouyang, Bingtong Wu, Haiyan Yu, Bo Dong
Summary: This study discovered the co-existence of endocytosis and exocytosis activities in the apical membrane during lumen formation and expansion in Ciona notochord. DYRK1 was found to regulate endocytosis through phosphorylation, which is required for lumen expansion. The findings suggest that a dynamic balance between endocytosis and exocytosis is crucial for maintaining apical membrane homeostasis and lumen growth and expansion in tubular organogenesis.
BIOLOGICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Baoye He, Huan Wang, Guosheng Liu, Angela Chen, Alejandra Calvo, Qiang Cai, Hailing Jin
Summary: Fungal pathogen Botrytis cinerea secretes sRNAs via extracellular vesicles (EVs) and these sRNAs enter plant cells through clathrin-mediated endocytosis (CME). EV biomarker BcPLS1 is crucial in this process. Knockout and dominant-negative mutants of CME pathway components in plants show increased resistance to Botrytis cinerea infection.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Mi Ke, Xiao Yuan, An He, Peiyuan Yu, Wendong Chen, Yu Shi, Tony Hunter, Peng Zou, Ruijun Tian
Summary: By developing more selective proximity labeling probes and combining them with label-free quantitative proteomics, the study enables exploration of cytosolic protein assemblies, such as phosphotyrosine-mediated protein complexes formed in response to minute-scale EGF stimulation. The authors demonstrate the application of this method in profiling the spatiotemporal interactome of the EGFR signaling component STS1.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Hannie Kremer
Summary: Despite decades of research, there is still much to be explored in the genetic landscape of sensorineural hearing loss. Finding new genes and uncovering the 'secrets' of known genes are essential for improving genetic diagnostics and developing therapeutic strategies. Collaborative studies and maximizing the use of available tools and resources are crucial for accelerating these discoveries.
Article
Cell Biology
Rachel E. Turn, Yihan Hu, Skylar Dewees, Narra Devi, Michael P. East, Katherine R. Hardin, Tala Khatib, Joshua Linnert, Uwe Wolfrum, Michael J. Lim, James E. Casanova, Tamara Caspary, Richard A. Kahn
Summary: ELMODs are a family of proteins that regulate the activity of a variety of GTPases. This study investigated the functions of ELMOD1 and ELMOD3 and compared them to the functions of ELMOD2. Deletion of ELMOD1 or ELMOD3 resulted in impaired primary cilium formation and protein trafficking from the Golgi to cilia. These phenotypes were reversed by activating mutant expression of ARL3 or ARL16.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Anatomy & Morphology
Sarah M. Kamel, Sanne Broekman, Federico Tessadori, Erwin van Wijk, Jeroen Bakkers
Summary: This study demonstrates the importance of Sgo1 in organ development and function using a zebrafish model, and reveals that its mutation may lead to abnormal cardiac function, impaired vision, and reduced food intake.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Medicine, Research & Experimental
Sophia Grotz, Jessica Schaefer, Kirsten A. Wunderlich, Zdenka Ellederova, Hannah Auch, Andrea Baehr, Petra Runa-Vochozkova, Janet Fadl, Vanessa Arnold, Taras Ardan, Miroslav Veith, Gianluca Santamaria, Georg Dhom, Wolfgang Hitzl, Barbara Kessler, Christian Eckardt, Joshua Klein, Anna Brymova, Joshua Linnert, Mayuko Kurome, Valeri Zakharchenko, Andrea Fischer, Andreas Blutke, Anna Doering, Stepanka Suchankova, Jiri Popelar, Eduardo Rodriguez-Bocanegra, Julia Dlugaiczyk, Hans Straka, Helen May-Simera, Weiwei Wang, Karl-Ludwig Laugwitz, Luk H. Vandenberghe, Eckhard Wolf, Kerstin Nagel-Wolfrum, Tobias Peters, Jan Motlik, M. Dominik Fischer, Uwe Wolfrum, Nikolai Klymiuk
Summary: This study generated the first translational animal model for Usher syndrome type 1, which exhibits characteristics of hearing loss, vestibular dysfunction, and visual impairment similar to human patients. The research also confirmed the therapeutic potential of gene repair and gene therapy for Usher syndrome through in vitro assessments using primary cells from Usher syndrome pigs or patients.
EMBO MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Ailis L. Moran, Stephen P. Carter, Joanna J. Kaylor, Zhichun Jiang, Sanne Broekman, Eugene T. Dillon, Alicia Gomez Sanchez, Sajal K. Minhas, Erwin van Wijk, Roxana A. Radu, Gabriel H. Travis, Michelle Carey, Oliver E. Blacque, Breandan N. Kennedy
Summary: The study reveals the importance of Rab28 in regulating both dawn and dusk peaks of outer segment phagocytosis (OSP). Loss of Rab28 leads to dysregulation of factors associated with OSP and perturbs the visual cycle. Transgenic overexpression of Rab28 in zebrafish cones rescues the OSP defect, highlighting the role of Rab28 in regulating OSP.
Article
Audiology & Speech-Language Pathology
Katelyn N. Robillard, Erik de Vrieze, Erwin van Wijk, Jennifer J. Lentz
Summary: Hearing loss, affecting over 430 million people worldwide, has significant impacts on physical, cognitive, and overall well-being. Antisense oligonucleotide (ASO)-based therapies show promise in treating hereditary hearing loss disorders by manipulating gene expression and targeting specific genetic factors.
Article
Biochemistry & Molecular Biology
Barbara Knapp, Jens Roedig, Heiko Roedig, Jacek Krzysko, Nicola Horn, Baran E. Gueler, Deva Krupakar Kusuluri, Adem Yildirim, Karsten Boldt, Marius Ueffing, Ines Liebscher, Uwe Wolfrum
Summary: In this study, novel protein networks and functional cellular modules associated with VLGR1 were identified using affinity proteomics. The findings provide new insights into the possible functions of VLGR1, related to the development of Usher syndrome, epilepsy, and other neuronal diseases.
Article
Biochemical Research Methods
R. T. W. Schellens, R. W. N. Slijkerman, L. Hetterschijt, T. A. Peters, S. Broekman, A. Clement, M. Westerfield, J. B. Phillips, K. Boldt, H. Kremer, E. De Vrieze, E. Van Wijk
Summary: In this study, whirlin-associated protein complexes were isolated and characterized from zebrafish photoreceptor cells. 19 novel candidate associated proteins were identified, and the association of 7 proteins with WHRN was confirmed. These findings suggest a role for whirlin in the photoreceptor synapse and provide insight into the molecular pathogenesis of Usher syndrome type 2.
JOURNAL OF PROTEOMICS
(2022)
Article
Genetics & Heredity
Janine Reurink, Erik de Vrieze, Catherina H. Z. Li, Emma van Berkel, Sanne Broekman, Marco Aben, Theo Peters, Jaap Oostrik, Kornelia Neveling, Hanka Venselaar, Mariana Guimaraes Ramos, Christian Gilissen, Galuh D. N. Astuti, Jordi Corominas Galbany, Janneke J. C. van Lith-Verhoeven, Charlotte W. Ockeloen, Lonneke Haer-Wigman, Carel B. Hoyng, Frans P. M. Cremers, Hannie Kremer, Susanne Roosing, Erwin van Wijk
Summary: The pathogenicity of the USH2A c.2276 G > T variant as a common cause of autosomal recessive retinitis pigmentosa was confirmed through genetic and functional analyses. A zebrafish model was generated to validate the findings. This study has significant implications for genetic diagnosis and future treatment options for this disease.
NPJ GENOMIC MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Kerstin Nagel-Wolfrum, Benjamin R. Fadl, Mirjana M. Becker, Kirsten A. Wunderlich, Jessica Schaefer, Daniel Sturm, Jacques Fritze, Burcu Guer, Lew Kaplan, Tommaso Andreani, Tobias Goldmann, Matthew Brooks, Margaret R. Starostik, Anagha Lokhande, Melissa Apel, Karl R. Fath, Katarina Stingl, Susanne Kohl, Margaret M. DeAngelis, Ursula Schlotzer-Schrehardt, Ivana K. Kim, Leah A. Owen, Jan M. Vetter, Norbert Pfeiffer, Miguel A. Andrade-Navarro, Antje Grosche, Anand Swaroop, Uwe Wolfrum
Summary: Usher syndrome (USH) is a common genetic disorder causing deaf-blindness. This study explores the role of harmonin protein in the pathophysiology of USH1C in the human eye. The localization and expression of harmonin in various retinal cells are correlated with the clinical phenotype observed in USH1C patients. Additionally, the study shows the potential of using harmonin_a1 transcript isoform for gene therapy treatment in USH1C patients.
HUMAN MOLECULAR GENETICS
(2023)
Article
Pharmacology & Pharmacy
Baran E. Gueler, Joshua Linnert, Uwe Wolfrum
Summary: VLGR1/ADGRV1 is a large adhesion G protein-coupled receptor associated with Usher syndrome, epilepsy, and other diseases. It is expressed widely in the CNS, eye, and inner ear. Previous research has shown that VLGR1 plays a role in focal adhesion dynamics and cell migration. This study aimed to elucidate the mechanisms of VLGR1 in focal adhesion turnover.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Pharmacology & Pharmacy
Joshua Linnert, Baran E. Gueler, Jacek Krzysko, Uwe Wolfrum
Summary: VLGR1/ADGRV1 is the largest known adhesion G protein-coupled receptor, and mutations in VLGR1/ADGRV1 are associated with Usher syndrome and epilepsy. This study identified autophagosomes as potential interacting proteins of VLGR1 and revealed the molecular and functional interaction between VLGR1 and key components of the autophagy process. These findings provide insights into the pathomechanisms underlying human USH and epilepsy related to VLGR1 defects.
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
(2023)
Article
Genetics & Heredity
Hedwig M. M. Velde, Xanne J. J. Huizenga, Helger G. G. Yntema, Lonneke Haer-Wigman, Andy J. J. Beynon, Jaap Oostrik, Sjoert A. H. Pegge, Hannie Kremer, Cris P. P. Lanting, Ronald J. E. Pennings
Summary: The aim of this study is to describe the genotype and phenotype of a Dutch-German family with DFNA6/14/38-related hearing loss and suggest screenings for newborns in such families. A novel likely pathogenic WFS1 variant was found to co-segregate with the hearing loss in the family. The study also revealed indications of mild vestibular dysfunction in affected individuals.
Article
Cell Biology
Joshua Linnert, Barbara Knapp, Baran E. Gueler, Karsten Boldt, Marius Ueffing, Uwe Wolfrum
Summary: The human Usher syndrome is characterized by progressive vision and hearing loss. Mutations in ADGRV1 and CIB2 genes are associated with two sub-types of Usher syndrome. The proteins encoded by these two genes belong to distinct protein families. The cellular functions of ADGRV1 and CIB2 are still unclear, but they are found to interact with each other and play a role in primary cilia function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Jessica Schaefer, Nicole Wenck, Katharina Janik, Joshua Linnert, Katarina Stingl, Susanne Kohl, Kerstin Nagel-Wolfrum, Uwe Wolfrum
Summary: Human Usher syndrome (USH) is a complex genetic disorder that causes combined deafness and blindness. The underlying mechanisms of the disease, particularly in the eye and retina, are not well understood. This study identifies a role for the scaffold protein harmonin, encoded by the USH1C gene, in regulating the canonical Wnt/beta-catenin signaling pathway. The findings suggest that USH1C/harmonin acts as a suppressor of the pathway, and dysregulation of this pathway may contribute to the development of USH.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)