Article
Multidisciplinary Sciences
Tian Xie, Guangjun Xu, Yun Liu, Bradley Quade, Weichun Lin, Xiao-chen Bai
Summary: MuSK is a receptor tyrosine kinase that is essential for the neuromuscular junction. Its activation requires both agrin and LRP4 coreceptors. This study presents the cryo-EM structure of the extracellular ternary complex of agrin/LRP4/MuSK, revealing how LRP4 recruits agrin and MuSK to activate MuSK receptor.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Tian Xie, Guangjun Xu, Yun Liu, Bradley Quade, Weichun Lin, Xiao-chen Bai
Summary: MuSK is a receptor tyrosine kinase that plays a crucial role in the formation and maintenance of the neuromuscular junction. This study reveals the structure of the agrin/LRP4/MuSK ternary complex and uncovers the mechanism of how agrin and LRP4 coactivate the MuSK receptor.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Hongyang Jing, Peng Chen, Tiankun Hui, Zheng Yu, Jin Zhou, Erkang Fei, Shunqi Wang, Dongyan Ren, Xinsheng Lai, Baoming Li
Summary: This study demonstrates that synapse-specific enrichment of Lrp4 mRNA requires a coordinated interaction between Lrp4/MuSK signaling, muscle activity, and Wnt non-canonical signaling. The findings provide a new mechanism for Lrp4 mRNA enrichment and a potential target for the treatment of NMJ aging and other NMJ-related diseases.
CELL AND BIOSCIENCE
(2021)
Article
Biotechnology & Applied Microbiology
Sangwook Oh, Xuming Mao, Silvio Manfredo-Vieira, Jinmin Lee, Darshil Patel, Eun Jung Choi, Andrea Alvarado, Ebony Cottman-Thomas, Damian Maseda, Patricia Y. Y. Tsao, Christoph T. T. Ellebrecht, Sami L. L. Khella, David P. P. Richman, Kevin C. C. O'Connor, Uri Herzberg, Gwendolyn K. K. Binder, Michael C. C. Milone, Samik Basu, Aimee S. S. Payne
Summary: Engineered T cells expressing MuSK-CAART effectively target B cells expressing anti-MuSK autoantibodies, reducing muscle weakness caused by autoimmune disease.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Katarina Gros, Urska Matkovic, Giulia Parato, Katarina Mis, Elisa Luin, Annalisa Bernareggi, Marina Sciancalepore, Tomaz Mars, Paola Lorenzon, Sergej Pirkmajer
Summary: Neuronal agrin has an age-dependent role in promoting the proliferation of human myoblasts by binding to Lrp4 and activating MuSK.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Developmental Biology
Lauren J. Walker, Rebecca A. Roque, Maria F. Navarro, Michael Granato
Summary: Using a zebrafish pectoral fin model, the study shows similarities in the development of neuromuscular synapses between axial and appendicular muscles, but differences in the MuSK, Agrin, and Lrp4 signaling pathways. This highlights distinct differences between axial and appendicular synapse development.
Article
Neurosciences
Dana L. E. Vergoossen, Arlin Keo, Ahmed Mahfouz, Maartje G. Huijbers
Summary: Myasthenia gravis (MG) is an acquired autoimmune disorder characterized by antibodies inhibiting neuromuscular transmission and potentially affecting the central nervous system. Expression analysis of MG-related genes in various tissues and brain regions revealed their potential roles outside skeletal muscle.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Svetlana Katchkovsky, Biplab Chatterjee, Chen-Viki Abramovitch-Dahan, Niv Papo, Noam Levaot
Summary: The binding of sclerostin (Scl) to its receptors, low-density lipoprotein receptor-related proteins 5 or 6 (LRP5/6), inhibits the induction of bone formation by Wnt ligands. It has been recently discovered that Scl binding to the co-receptor LRP4 enhances this inhibition. Using the yeast display system, this study demonstrates that Scl has a stronger binding affinity for LRP4 than for LRP6, and the presence of LRP4 enhances Scl binding to LRP6. Furthermore, the study shows that the binding of Scl to LRP4 is crucial for its inhibition of the Wnt pathway. The findings suggest that compounds targeting Scl-LRP4 interactions could be potential strategies for promoting anabolic bone functions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Endocrinology & Metabolism
Nigel Kurgan, Joshua Stoikos, Bradley J. Baranowski, Jenalyn Yumol, Roopan Dhaliwal, Jake B. Sweezey-Munroe, Val A. Fajardo, William Gittings, Rebecca E. K. Macpherson, Panagiota Klentrou
Summary: This study examined the effects of exercise training on sclerostin content and its relationship with body composition and whole-body metabolism. The results showed that exercise training reduced sclerostin content in subcutaneous white adipose tissue and was associated with changes in body fat and energy metabolism.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Cell Biology
Shuang Geng, Fabian Paul, Izabela Kowalczyk, Sandra Raimundo, Anje Sporbert, Tamrat Meshka Mamo, Annette Hammes
Summary: In this study, the role of LRP4 in regulating WNT signalling during early mouse forebrain development was investigated. The results show that LRP4 is crucial for accurate neural tube morphogenesis and modulates LRP5- and LRP6-mediated WNT signalling. These findings provide insights into the mechanisms of how LRPs participate in controlling WNT signalling.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Medicine, General & Internal
Rika Yamashita, Mikito Shimizu, Kousuke Baba, Goichi Beck, Makoto Kinoshita, Tatsusada Okuno, Osamu Higuchi, Hideki Mochizuki
Summary: This case report presents a 62-year-old patient with MG who tested positive for anti-MuSK antibodies, as well as anti-Lrp4 and anti-titin antibodies. The patient had a history of intermittent double vision and ptosis for 10 years, which eventually led to MG crisis, showcasing the unique characteristics of anti-MuSK-antibody positive MG accompanied by anti-Lrp4 and anti-titin antibodies.
Review
Neurosciences
Victoria N. Alexander
Summary: This paper explores the possibility of irrational cognition in aneural cells and discusses three examples of irrational learning in such cells. It suggests that aneural cells may use semiotic qualities to overcome old algorithms and find creative solutions.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Chemistry, Multidisciplinary
Nirosha J. Murugan, Daniel H. Kaltman, Paul H. Jin, Melanie Chien, Ramses Martinez, Cuong Q. Nguyen, Anna Kane, Richard Novak, Donald E. Ingber, Michael Levin
Summary: The unicellular protist Physarum polycephalum demonstrates an ability to use mechanosensation for decision-making, preferentially growing towards heavier, substrate-deforming objects. It is shown that Physarum may calculate by sensing the fraction of its perimeter distorted above a threshold substrate strain, enabling long-range decisions based on biomechanical features. These findings highlight a unique method of mechanosensation and how this aneural organism adapts to its environment.
ADVANCED MATERIALS
(2021)
Article
Genetics & Heredity
Yentl Huybrechts, Eveline Boudin, Gretl Hendrickx, Ellen Steenackers, Neveen Hamdy, Geert Mortier, Guillermo Martinez Diaz-Guerra, Milagros Sierra Bracamonte, Natasha M. Appelman-Dijkstra, Wim Van Hul
Summary: Sclerosteosis is a high bone mass disorder caused by pathogenic variants in the genes encoding sclerostin or LRP4. This study demonstrates that a pathogenic variant in the first beta-propeller domain of LRP4 can contribute to the development of sclerosteosis.
Article
Neurosciences
Ryan Massopust, Devin Juros, Dillon Shapiro, Mikayla Lopes, Saptarsi M. Haldar, Thomas Taetzsch, Gregorio Valdez
Summary: Muscle-specific KLF15 overexpression does not have a significant beneficial effect on the disease progression of SOD1(G93A) ALS mice, unlike in mouse models of DMD and SMA.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
Arnab Barik, Lei Li, Anupama Sathyamurthy, Wen-Cheng Xiong, Lin Mei
JOURNAL OF NEUROSCIENCE
(2016)
Article
Neurosciences
Lei Li, Yu Cao, Haitao Wu, Xinchun Ye, Zhihui Zhu, Guanglin Xing, Chengyong Shen, Arnab Barik, Bin Zhang, Xiaoling Xie, Wenbo Zhi, Lin Gan, Huabo Su, Wen-Cheng Xiong, Lin Mei
Article
Neurosciences
Nima Ghitani, Arnab Barik, Marcin Szczot, James H. Thompson, Chia Li, Claire E. Le Pichon, Michael J. Krashes, Alexander T. Chesler
Article
Neurosciences
Thiri W. Lin, Zhibing Tan, Arnab Barik, Dong-Min Yin, Egil Brudvik, Hongsheng Wang, Wen-Cheng Xiong, Lin Mei
JOURNAL OF NEUROSCIENCE
(2018)
Article
Biology
Chengyong Shen, Lei Li, Kai Zhao, Lei Bai, Ailian Wang, Xiaoqiu Shu, Yatao Xiao, Jianmin Zhang, Kejing Zhang, Tiankun Hui, Wenbing Chen, Bin Zhang, Wei Hsu, Wen-Cheng Xiong, Lin Mei
Article
Neurosciences
Arnab Barik, James Hunter Thompson, Mathew Seltzer, Nima Ghitani, Alexander T. Chesler
Editorial Material
Neurosciences
Arnab Barik, Michael J. Krashes
Article
Cell Biology
Marcin Szczot, Jaquette Liljencrantz, Nima Ghitani, Arnab Barik, Ruby Lam, James H. Thompson, Diana Bharucha-Goebel, Dimah Saade, Aaron Necaise, Sandra Donkervoort, A. Reghan Foley, Taylor Gordon, Laura Case, M. Catherine Bushnell, Carsten G. Bonnemann, Alexander T. Chesler
SCIENCE TRANSLATIONAL MEDICINE
(2018)
Article
Cell Biology
Hans Jurgen Solinski, Mette C. Kriegbaum, Pang-Yen Tseng, Thomas W. Eamest, Xinglong Gu, Arnab Barik, Alexander T. Chesler, Mark A. Hoon
Article
Genetics & Heredity
Julia Kozlitina, Davide Risso, Katherine Lansu, Reid Hans Johnson Olsen, Eduardo Sainz, Donata Luiselli, Arnab Barik, Carlos Frigerio-Domingues, Luca Pagani, Stephen Wooding, Thomas Kirchner, Ray Niaura, Bryan Roth, Dennis Drayna
Article
Biochemistry & Molecular Biology
Beibei Wang, Yang Li, Ming Sui, Qinqin Qi, Ting Wang, Dan Liu, Meiling Zhou, Yunjie Zheng, Ling-Qiang Zhu, Bin Zhang
Article
Cell Biology
Anupama Sathyamurthy, Arnab Barik, Courtney Dobrott, Kaya J. E. Matson, Stefan Stoica, Randall Pursley, Alexander T. Chesler, Ariel J. Levine
Editorial Material
Neurosciences
Arnab Barik, Alexander T. Chesler
Article
Biology
Arnab Barik, Anupama Sathyamurthy, James Thompson, Mathew Seltzer, Ariel Levine, Alexander Chesler
Summary: The pathway from spinal cord to brain for ongoing pain involves activation of spinal neurons expressing Tacr1, leading to pain-related behaviors. PBN-SLTacr1 neurons respond to sustained stimuli, enhancing nocifensive behaviors and suppressing itch, while their silencing causes mice to ignore long-lasting noxious stimuli. This spinoparabrachial pathway plays a key role in the sensation of ongoing pain.
Review
Neurosciences
Devanshi Piyush Shah, Arnab Barik
Summary: This review focuses on recent findings that shed light on the neural pathways involved in itch-induced scratching. Comparisons are made between the molecularly defined itch pathways and known pain circuits. Roles played by neurons in the spinoparabrachial pathway are reviewed, as well as the implications of scratching as a behavioral measure for itch intensity and understanding underlying supraspinal mechanisms.
FRONTIERS IN NEURAL CIRCUITS
(2022)