Review
Neurosciences
Davide Bassetti
Summary: Gamma-aminobutyric acid (GABA) is the main neurotransmitter in the brain responsible for inhibiting neuronal activity. GABA(B) receptors play a crucial role in regulating proliferation, migration, and cell inhibition. They can shape neuronal activity and contribute to development by modulating the function of cells in response to varying levels of GABA concentration.
Article
Multidisciplinary Sciences
David H. Brookes, Amirali Aghazadeh, Jennifer Listgarten
Summary: Fitness functions map biological sequences to specific properties, but accurately estimating these functions with limited data is a challenge. This study develops a framework to investigate the sparsity of fitness functions sampled from the GNK model and validates its effectiveness.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Multidisciplinary Sciences
Hamidreza Shaye, Benjamin Stauch, Cornelius Gati, Vadim Cherezov
Summary: GABA(B) receptors play a crucial role in inhibitory neurotransmission in the brain, modulating neuronal signaling and being linked to various neurological disorders. Recent cryo-EM studies have provided detailed insights into the activation mechanism of GABA(B) receptors, offering potential for the discovery of new therapeutic drugs and neuromodulators. The structures of the receptor in different conformational states and bound to various ligands contribute to a comprehensive understanding of the receptor's activation process.
Review
Cell Biology
Llara Prieto-Fernandez, Sofia T. Menendez, Maria Otero-Rosales, Irene Montoro-Jimenez, Francisco Hermida-Prado, Juana M. Garcia-Pedrero, Saul Alvarez-Teijeiro
Summary: This article reviews the dysfunction of Annexins in cancer, including their expression levels, mechanisms of action, and pathophysiological effects, with a focus on head and neck cancers. Annexins exhibit varying expression levels and phenotypic specificity in different types of cancer.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Cangsong Shen, Chunyou Mao, Chanjuan Xu, Nan Jin, Huibing Zhang, Dan-Dan Shen, Qingya Shen, Xiaomei Wang, Tingjun Hou, Zhong Chen, Philippe Rondard, Jean-Philippe Pin, Yan Zhang, Jianfeng Liu
Summary: This study reveals the structure of a class-C heterodimeric GABA(B) receptor in its active form complexed with Gi1 protein, showing a unique binding mode of G protein interaction compared to other classes of GPCR. The active form of the transmembrane domain of this GABA(B) receptor differs from that of other GPCRs, leading to distinctive inter- and intra-subunit changes linked to agonist binding and G-protein activation in this heterodimeric complex.
Review
Oncology
Yucheng Dong, Qi He, Xinyu Chen, Fan Yang, Li He, Yongchang Zheng
Summary: Extrachromosomal DNA (ecDNA) is circular DNA that plays a significant role in cancer development and heterogeneity. Advances in detection methods, such as microscopy and sequencing, have greatly improved our understanding of ecDNA's molecular characteristics, functions, mechanisms of formation, and clinical implications in cancer. This review focuses on the role of ecDNA in acquired drug resistance, its potential as a diagnostic and prognostic biomarker, and its significance as a therapeutic target in cancer.
FRONTIERS IN ONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Akiyo Yoshimura, Issei Imoto, Hiroji Iwata
Summary: Approximately 5-10% of breast cancer cases are caused by germline pathogenic variants in cancer predisposition genes. BRCA1 and BRCA2 are the most common genes associated with hereditary breast cancer. Other genes such as ATM, BARD1, CHEK2, PALB2, RAD51C, and RAD51D have also been identified as having moderate to high risk of breast cancer. The optimal preventive strategies for most hereditary breast cancers are still undetermined. Understanding the functions of breast cancer-associated genes can help estimate genetic risk and guide preventive and therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Pascal Dominic Rem, Vita Sereikaite, Diego Fernandez-Fernandez, Sebastian Reinartz, Daniel Ulrich, Thorsten Fritzius, Luca Trovo, Salome Roux, Ziyang Chen, Philippe Rondard, Jean-Philippe Pin, Jochen Schwenk, Bernd Fakler, Martin Gassmann, Tania Rinaldi Barkat, Kristian Stromgaard, Bernhard Bettler
Summary: Amyloid-beta precursor protein (APP) regulates neuronal activity through the release of secreted APP (sAPP) acting at cell surface receptors. A 17 amino acid peptide (APP17) derived from APP binds to the extracellular sushi domain 1 (SD1) of GABA(B) receptors (GBRs). However, APP17 does not influence GBR activity in heterologous cells, indicating that sAPP exerts its neuronal effects through receptors other than GBRs.
Review
Cell Biology
Lei Liu, Li Lin, Cangsong Shen, Philippe Rondard, Jean-Philippe Pin, Chanjuan Xu, Jianfeng Liu
Summary: c-aminobutyric acid type B (GABAB) and metabotropic glutamate (mGlu) receptors are important drug targets as the largest family of membrane proteins known as G protein-coupled receptors (GPCRs). Both GABAB and mGlu receptors require quaternary structures for their function as mandatory dimers. The recent structures of these receptors in different conformations and in complexes with G proteins have revealed their asymmetric activation. The discovery of specific and functional mGlu heterodimers further highlights this asymmetry. The development of allosteric modulators targeting the transmembrane interface presents new opportunities for modulating the function of these receptors.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Cell Biology
Sharon Negri, Francesca Scolari, Mauro Vismara, Valentina Brunetti, Pawan Faris, Giulia Terribile, Giulio Sancini, Roberto Berra-Romani, Francesco Moccia
Summary: This study reveals the molecular mechanisms by which GABA controls endothelial signaling at the neurovascular unit through activating GABA(A) and GABA(B) receptors, and involves multiple signaling pathways, which is of great significance for understanding the function of GABA in the neurovascular unit.
Review
Oncology
Jiajia Li, Liyao Peng, Qun Chen, Ziping Ye, Tiantian Zhao, Sicong Hou, Jianguo Gu, Qinglei Hang
Summary: Pancreatic cancer is a rapidly progressing disease with high mortality. Current treatment methods include surgery, radiotherapy, and chemotherapy, but the survival rate remains disappointing. Therefore, understanding the molecular mechanisms and developing targeted drugs are crucial for improving prognosis. Integrin beta 1, a common beta subunit of the integrin family, has been found to be closely related to vascular invasion, distant metastasis, and survival in pancreatic cancer patients, and targeted treatment with integrin beta 1 has shown initial success in animal models. This review summarizes the signaling pathways involving integrins in pancreatic cancer and focuses on the role of integrin beta 1 in the malignant behaviors of pancreatic cancer. The feasibility of integrin beta 1 as a diagnostic and prognostic biomarker in pancreatic cancer is also discussed, along with the progress of several clinical trials targeting integrin beta 1.
Article
Biology
Pradeep Bhandari, David Vandael, Diego Fernandez-Fernandez, Thorsten Fritzius, David Kleindienst, Cihan Onal, Jacqueline Montanaro, Martin Gassmann, Peter Jonas, Akos Kulik, Bernhard Bettler, Ryuichi Shigemoto, Peter Koppensteiner
Summary: The study found that KCTD8 and KCTD12b directly bind to Cav2.3 and co-localize in the rostral IPN. These KCTDs modulate synaptic strength by regulating Cav2.3-mediated release, independent of GBR activation.
Review
Biochemistry & Molecular Biology
Wen-Jie Shu, Hai-Ning Du
Summary: SETD3 is a member of a family of proteins containing the SET domain, and it functions as a histidine methyltransferase catalyzing methylation of actin histidine 73. Recent research advances have focused on structural properties, substrate recognition features, and physiological functions, particularly highlighting the potential pathological relevance of SETD3 in human cancers.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Article
Neurosciences
Alessandra Porcu, Rafaela Mostallino, Valeria Serra, Miriam Melis, Valeria Sogos, Sarah Beggiato, Luca Ferraro, Fabrizio Manetti, Beatrice Gianibbi, Bernhard Bettler, Federico Corelli, Claudia Mugnaini, M. Paola Castelli
Summary: This study characterized the negative allosteric modulator COR758 for GABA(B) receptors, showing its potential as a therapeutic candidate by inhibiting G protein signaling. COR758 may serve as a scaffold for developing additional NAMs for therapeutic intervention by interacting with an allosteric binding site of GABA(B) receptors.
Article
Endocrinology & Metabolism
Noelia P. Di Giorgio, Marianne Bizzozzero-Hiriart, Pablo N. Surkin, Esteban Repetto, Maria M. Bonaventura, Florencia N. Tabares, Nadia S. Bourguignon, Ayelen Converti, Juan M. Riano Gomez, Bernhard Bettler, Victoria Lux-Lantos
Summary: GABA and Kisspeptin play critical roles in reproduction and metabolic control. A unique mouse lacking GABAB receptors in Kiss1 cells showed severe impairment in glucose homeostasis, which worsened with aging. These results reinforce the involvement of Kisspeptin in metabolic regulation and highlight the importance of GABA through GABAB receptors in the regulation of the peripheral pancreas Kisspeptin system.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)