Review
Cell Biology
Ian James Bell, Matthew Sheldon Horn, Terence John Van Raay
Summary: The non-canonical Wnt signaling pathways have different roles in cancer and development, involving calcium and Vangl2. Cells tend to choose non-canonical Wnt signaling over canonical Wnt signaling when presented with a choice, but this occurs rarely in vivo.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Francesca Manuela Johnson de Sousa Brito, Andrew Butcher, Addolorata Pisconti, Blandine Poulet, Amanda Prior, Gemma Charlesworth, Catherine Sperinck, Michele Scotto di Mase, Ke Liu, George Bou-Gharios, Robert Jurgen van 't Hof, Anna Daroszewska
Summary: Syndecan-3 promotes new bone formation in osteoblasts by enhancing WNT signaling, and its deficiency in mice results in an early osteoporosis-like phenotype due to delayed osteoblast maturation and impaired function. Overexpressing Sdc3 in osteoblasts rescues the low bone volume phenotype and increases bone mass, making SDC3 a potential target for novel bone anabolic drug development.
Article
Biochemistry & Molecular Biology
Emily P. Y. Yu, Vishal Saxena, Sofia Perin, Marc Ekker
Summary: The dlx genes encode transcription factors that play important roles in craniofacial development. Mutations in dlx5a and dlx5i6 were found to lead to shortened cartilage lengths and altered proliferation of neural crest cells. These mutations also affected the non-canonical Wnt signaling pathway.
Article
Biochemistry & Molecular Biology
Ilija Perutina, Nela Kelam, Mirko Maglica, Anita Racetin, Marin Ogorevc, Natalija Filipovic, Yu Katsuyama, Josip Miskovic, Katarina Vukojevic
Summary: This study determines the protein expression patterns of several proteins in developing and early postnatal kidneys of yotari mice and their role in regulating the Wnt signaling pathway. The study finds that the expression of these proteins is crucial for normal nephrogenesis and suggests that the defective Dab1 gene in yotari mice may promote congenital anomalies of kidney and urinary tract (CAKUT) by interfering with this process.
Article
Biology
Andrew M. Hamilton, Olga A. Balashova, Laura N. Borodinsky
Summary: Research indicates that Hedgehog (Hh) signaling may be a useful target for driving regeneration, and non-canonical mechanisms of Hh signaling are necessary for spinal cord and muscle regeneration.
Article
Cell Biology
Andre Landin Malt, Shaylyn Clancy, Diane Hwang, Alice Liu, Connor Smith, Margaret Smith, Maya Hatley, Christopher Clemens, Xiaowei Lu
Summary: A non-canonical Wnt signaling pathway has been found to promote cochlear outgrowth and coordinate planar polarization of hair cells. Gsk3 beta and Rac1 play crucial roles in this pathway, as shown in genetic rescue experiments.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Urology & Nephrology
Dong Zhou, Yuanyuan Wang, Yuan Gui, Haiyan Fu, Shanshan Zhou, Yanlin Wang, Sheldon I. Bastacky, Donna B. Stolz, Youhua Liu
Summary: Podocyte-derived Wnts play an important role in protecting podocytes from injury by repressing b-catenin via activating non-canonical Wnt/calcium signaling.
KIDNEY INTERNATIONAL
(2022)
Review
Ophthalmology
Ruchi Shah, Cynthia Amador, Steven T. Chun, Sean Ghiam, Mehrnoosh Saghizadeh, Andrei A. Kramerov, Alexander Ljubimov
Summary: Wnt signaling plays crucial roles in cell proliferation, differentiation, apoptosis, stem cell maintenance, and tissue homeostasis in the eye. It is classified into canonical (β-catenin-dependent) and noncanonical (β-catenin-independent) pathways. Previous studies have focused mainly on canonical Wnt signaling, while the role of noncanonical signaling and the crosstalk between canonical and noncanonical pathways in the eye are poorly understood. This review provides an overview of ocular noncanonical Wnt signaling, including its developmental and functional aspects in different eye compartments. It also discusses the significant changes of this signaling in various ocular conditions.
PROGRESS IN RETINAL AND EYE RESEARCH
(2023)
Article
Cell Biology
Mukulika Bose, Priyanka Grover, Alexa J. Sanders, Ru Zhou, Mohammad Ahmad, Sophia Shwartz, Priyanka Lala, Sritama Nath, Mahboubeh Yazdanifar, Cory Brouwer, Pinku Mukherjee
Summary: This study finds that MUC1 plays a significant role in the development of pancreatic ductal adenocarcinoma (PDA). Overexpression of MUC1 activates the JNK pathway and increases cell viability. Conversely, low expression of MUC1 allows TGF-beta to retain its tumor-suppressive function. These findings contribute to a better understanding of the mechanisms behind PDA development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Manman Liang, Lijing Wang, Zhengui Sun, Xingwu Chen, Hanli Wang, Lilong Qin, Wenying Zhao, Biao Geng
Summary: This study reveals that TRIM15 is frequently upregulated in NSCLC and associated with poor prognosis. Functionally, TRIM15 promotes proliferation and metastasis of NSCLC cells through its E3 ubiquitin ligase activity. Mechanistically, TRIM15 directly targets Keap1 and promotes its ubiquitination and degradation, resulting in the escape of Nrf2 from Keap1-mediated degradation, subsequently promoting antioxidant response and tumor progression.
CELL COMMUNICATION AND SIGNALING
(2022)
Article
Virology
Lei Hou, Xiaohan Hu, Jinshuo Guo, Rong Quan, Li Wei, Jing Wang, Jiangwei Song, Jue Liu
Summary: In this study, we found that aMPV/C infection induces MAVS degradation through the ubiquitin-proteasome pathway at the post-translational level. Furthermore, specific amino acid sites were identified as pivotal in the formation of polyubiquitin chains during MAVS degradation. E3 ubiquitin ligases targeting MAVS were also identified, with RNF5 shown to be involved in MAVS degradation in aMPV/C-infected cells.
Review
Biochemistry & Molecular Biology
Michal Tracz, Wojciech Bialek
Summary: Protein ubiquitination, initially known for its role in proteolysis, is now recognized as essential for various cellular processes. Different types of ubiquitin linkages, beyond the commonly studied K48- and K63-linked chains, are equally important and are receiving increasing attention in recent research.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2021)
Article
Behavioral Sciences
Rodrigo F. Narvaes, Eduarda G. Nachtigall, Lucas A. Marcondes, Ivan Izquierdo, Jociane de C. Myskiw, Cristiane R. G. Furini
Summary: This study found that both the canonical Wnt/β-catenin and non-canonical Wnt/Ca2+ signaling pathways are involved in fear memory retrieval, highlighting the importance of the medial prefrontal cortex in this process.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Multidisciplinary Sciences
Victoria H. Ng, Zachary Spencer, Leif R. Neitzel, Anmada Nayak, Matthew A. Loberg, Chen Shen, Sara N. Kassel, Heather K. Kroh, Zhenyi An, Christin C. Anthony, Jamal M. Bryant, Amanda Lawson, Lily Goldsmith, Hassina Benchabane, Amanda G. Hansen, Jingjing Li, Starina D'Souza, Andres M. Lebensohn, Rajat Rohatgi, William A. Weiss, Vivian L. Weiss, Charles Williams, Charles C. Hong, David J. Robbins, Yashi Ahmed, Ethan Lee
Summary: The study identifies the USP46 deubiquitylase complex as a positive regulator of Wnt signaling in various organisms. The complex inhibits the degradation of cell surface LRP6, thereby enhancing Wnt signaling. The authors propose a model for the assembly of the complex and its role in Wnt signaling.
NATURE COMMUNICATIONS
(2023)
Article
Engineering, Biomedical
Derek Avery, Lais Morandini, Luke S. Sheakley, Arth H. Shah, Loc Bui, Jefferson O. Abaricia, Rene Olivares-Navarrete
Summary: This study investigates the role of canonical Wnt signaling in the response of macrophages to titanium surface properties. The results show that activating canonical Wnt signaling promotes a pro-inflammatory phenotype, while inhibiting it enhances an anti-inflammatory response.
Article
Cell Biology
Francisco Bustos, Anna Segarra-Fas, Viduth K. Chaugule, Lennart Brandenburg, Emma Branigan, Rachel Toth, Thomas Macartney, Axel Knebel, Ronald T. Hay, Helen Walden, Greg M. Findlay
Article
Developmental Biology
Catalina Manieu, Gonzalo H. Olivares, Franco Vega-Macaya, Mauricio Valdivia, Patricio Olguin
MECHANISMS OF DEVELOPMENT
(2018)
Article
Genetics & Heredity
Benjamin Angulo, Shrividhya Srinivasan, Benjamin J. Bolival, Gonzalo H. Olivares, Allyson C. Spence, Margaret T. Fuller
Editorial Material
Biochemistry & Molecular Biology
Gonzalo H. Olivares, Patricio Olguin, Andres D. Klein
TRENDS IN MOLECULAR MEDICINE
(2019)
Article
Multidisciplinary Sciences
Rosalia Fernandez-Alonso, Francisco Bustos, Manon Budzyk, Pankaj Kumar, Andreas O. Helbig, Jens Hukelmann, Angus Lamond, Fredrik Lanner, Houjiang Zhou, Evangelia Petsalaki, Greg M. Findlay
NATURE COMMUNICATIONS
(2020)
Article
Cell Biology
Francisco Bustos, Anna Segarra-Fas, Gino Nardocci, Andrew Cassidy, Odetta Antico, Lindsay Davidson, Lennart Brandenburg, Thomas J. Macartney, Rachel Toth, C. James Hastie, Jennifer Moran, Robert Gourlay, Joby Varghese, Renata F. Soares, Martin Montecino, Greg M. Findlay
DEVELOPMENTAL CELL
(2020)
Article
Multidisciplinary Sciences
Ignacio Medina-Yanez, Gonzalo H. Olivares, Franco Vega-Macaya, Marek Mlodzik, Patricio Olguin
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Francisco Bustos, Carmen Espejo-Serrano, Anna Segarra-Fas, Rachel Toth, Alison J. Eaton, Kristin D. Kernohan, Meredith J. Wilson, Lisa G. Riley, Greg M. Findlay
Summary: TOKAS is an X-linked intellectual disability syndrome caused by variants in the gene encoding RLIM. A novel missense variant in RLIM disrupts protein expression and function, leading to a severe form of the syndrome. This variant impairs E3 ubiquitin ligase activity and disrupts X-chromosome inactivation.
SCIENTIFIC REPORTS
(2021)
Article
Cell & Tissue Engineering
Johany Penailillo, Miriam Palacios, Constanza Mounieres, Rosana Munoz, Paula G. Slater, Elena De Domenico, Ilya Patrushev, Mike Gilchrist, Juan Larrain
Summary: Xenopus laevis can regenerate the spinal cord during larvae stages by activating NSPCs. The mTOR signaling pathway plays a key role in the early steps of spinal cord regeneration.
NPJ REGENERATIVE MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Francisco Bustos, Greg M. Findlay
Summary: Intellectual disability (ID) is a major burden on healthcare systems in developed countries, but there is a gap between our understanding of genes mutated in ID and the molecular mechanisms underlying these disorders. Investigating the dysregulated signaling and transcriptional networks in patients may lead to new therapeutic opportunities.
Article
Biochemistry & Molecular Biology
Anna Segarra-Fas, Carmen Espejo-Serrano, Francisco Bustos, Houjiang Zhou, Feng Wang, Rachel Toth, Thomas Macartney, Ingolf Bach, Gino Nardocci, Greg M. Findlay
Summary: The study revealed that the ubiquitin ligase RNF12 plays a crucial role in mouse testes by regulating the deubiquitylase USP26 and influencing the transcriptional regulator REX1, which is essential for gametogenesis and germ cell differentiation.
Article
Biology
Francisco Bustos, Sunil Mathur, Carmen Espejo-Serrano, Rachel Toth, C. James Hastie, Satpal Virdee, Greg M. Findlay
Summary: This study utilized photocrosslinking activity-based probes to monitor the RING E3 ubiquitin ligase activity of RNF12 and demonstrated its application in assessing the impact of RNF12 variants on activity. The findings showed that the photoABPs accurately reported the effects of RNF12 variants on E3 activity, and the technology could be rapidly deployed in human pluripotent stem cells.
LIFE SCIENCE ALLIANCE
(2022)
Article
Clinical Neurology
Gonzalo H. Olivares, Franco Nunez-Villegas, Noemi Candia, Karen Orostica, M. Constanza Gonzalez-Ramirez, Franco Vega-Macaya, Nolberto Zuniga, Cristian Molina, Carlos Oliva, Trudy F. C. Mackay, Ricardo A. Verdugo, Patricio Olguin
Summary: The mechanisms by which genotype interacts with nutrition during development to influence complex behaviors and brain morphology are not well understood. This study used fruit flies to identify genes and pathways associated with sleep behavior and brain morphology in response to early-life nutrition. The researchers found that the effects of early-life nutritional restriction on sleep behavior and brain morphology depend on genotype. They identified genes involved in neural development, translation, and insulin signaling as important factors in the variable response of sleep and brain morphology to early-life nutrition.
Article
Biochemistry & Molecular Biology
J. M. Zuniga-Hernandez, Gonzalo H. Olivares, Patricio Olguin, Alvaro Glavic
Summary: Nutrient scarcity during development affects adult activity and sleep behavior in flies, along with changes in gene expression and epigenetic marks in the mushroom bodies (MBs). Open chromatin regions in the MBs correlate with increased expression of certain genes, particularly at the Dopamine 1-like receptor 2 regulatory zones. Inhibition of dopamine signaling or reduction of dop1R2 expression can reverse the behavioral effects caused by early-life nutrient restriction. These findings highlight the importance of dopamine signaling in regulating the effects of nutrient scarcity on behavior.
Article
Genetics & Heredity
Noemi Candia, Andres Ibacache, Ignacio Medina-Yanez, Gonzalo H. Olivares, Mauricio Ramirez, Franco Vega-Macaya, Andres Couve, Jimena Sierralta, Patricio Olguin
Summary: Hereditary spastic paraplegias (HSPs) are neurodegenerative disorders characterized by dysfunction of corticospinal motor neurons. Mutations in Atlastin1/Spg3 gene account for 10% of HSPs and patients with the same mutation show variability in age at onset and severity, indicating the involvement of environment and genetic background.