Article
Physiology
Yui Shibayama, Chantal Alkhoury, Ivan Nemazanyy, Nathaniel Henneman, Nicolas Cagnard, Muriel Girard, Tatsuya Atsumi, Ganna Panasyuk
Summary: Class 3 PI3K is crucial for corticosterone metabolism and GR transcriptional activity in the liver.
Review
Immunology
Ebru Aydin, Sebastian Faehling, Mariam Saleh, Laura Llao Cid, Martina Seiffert, Philipp M. Roessner
Summary: PI3K pathway plays a crucial role in cell growth and malignant transformation, with its hyperactivation being a hallmark of cancer. Inhibiting PI3K not only affects cancer cells but also impacts the tumor microenvironment and immune cell function. Understanding the effects of PI3K inhibition on the tumor microenvironment in CLL can lead to improved drug development and novel combinatory treatment strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Natasha M. Setiabakti, Pia Larsson, Justin R. Hamilton
Summary: Understanding the role of phosphoinositide 3-kinases (PI3Ks) in platelet function and thrombus formation is crucial for the development of therapeutic drugs for thrombotic cardiovascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Allergy
Jessica Oh, Elizabeth Garabedian, Ramsay Fuleihan, Charlotte Cunningham-Rundles
Summary: Activated phosphoinositide 3-kinase delta syndrome is a combined primary immunodeficiency characterized by various manifestations such as respiratory infections, lymphadenopathy, and developmental delay. Clinical features differ between PIK3CD and PIK3R1 patients, with a higher frequency of asthma observed in the PIK3CD cohort.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Review
Biochemistry & Molecular Biology
Kazuaki Yoshioka
Summary: PI3Ks are lipid kinases involved in regulating various cellular processes. Recent studies suggest that class II PI3K isoforms play important roles in clathrin-mediated endocytosis and endosomal signaling.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Review
Chemistry, Medicinal
Jingyu Zhu, Kan Li, Li Yu, Yun Chen, Yanfei Cai, Jian Jin, Tingjun Hou
Summary: Phosphatidylinositol 3-kinase gamma (PI3Kγ) is considered a promising drug target for various diseases, with the importance of isoform selectivity in development highlighted; this review provides an overview of the structural features influencing selectivity, discusses the structure-activity relationship of existing inhibitors, and summarizes experimental and computational techniques for inhibitor identification.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Cell Biology
Fatemeh Mazloumi Gavgani, Thomas Karlsson, Ingvild L. Tangen, Andrea Papdine Morovicz, Victoria Smith Arnesen, Diana C. Turcu, Sandra Ninzima, Katharina Spang, Camilla Krakstad, Julie Guillermet-Guibert, Aurelia E. Lewis
Summary: In tumors, the PI3K catalytic subunits p110 alpha and p110 beta are differently expressed and targeted. While PIK3CB is less mutated compared to PIK3CA, it may still contribute to tumorigenesis in PTEN-deficient tumors. The high levels of p110 beta in the nucleus and its nucleolar role in endometrial cancer cells suggest its potential involvement in tumorigenesis.
JOURNAL OF CELL SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Peter K. Vogt, Jonathan R. Hart, Su Yang, Qingtong Zhou, Dehua Yang, Ming-Wei Wang
Summary: Recent cryo-EM investigations have analyzed various structural conformations and functional states of PI3K, specifically its catalytic and regulatory subunits. High resolution structures of unliganded and BYL-719-bound PI3K have been obtained, providing insights into the flexible domains of the regulatory subunit. Mutations in the helical and kinase domains of the catalytic subunit have also been studied, revealing mutant-specific features related to enzymatic and signaling activities.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Pharmacology & Pharmacy
Ava Safaroghli-Azar, Mohammad-Javad Sanaei, Atieh Pourbagheri-Sigaroodi, Davood Bashash
Summary: Lipid signaling refers to the biological process in which a lipid messenger binds to a protein target, converting its effects to specific cellular responses. The family of phosphoinositide 3-kinase (PI3K) plays a crucial role in this pathway, affecting various aspects of cellular biology such as cell survival, proliferation, migration, endocytosis, intracellular trafficking, metabolism, and autophagy. Different classes of PI3Ks have been identified in yeast and mammals, with class I PI3Ks being extensively studied in cancer biology. Abnormal activation of class I PI3Ks has been implicated in human tumors, particularly through activating mutations in the PIK3CA gene. Class II and III PI3Ks are involved in regulating vesicle trafficking and autophagy processes. This review aims to discuss the latest research findings on PI3Ks-mediated cell biological processes and explore the mechanisms by which different types of phosphoinositides derived from PI3Ks act.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Physical
Xiaoniu Fang, Ya Gao, Chen Wang, Huimin Chen, Tong Zhu
Summary: This study combined MD simulations and binding affinity calculations to elucidate the interaction mechanism of different inhibitors towards PI3K subtypes, pointing out the critical roles of key residues, hydrophobic interactions, and hydrogen bonds in understanding binding selectivity. The findings can serve as a theoretical reference for the design of more promising selective inhibitors.
CHEMICAL PHYSICS LETTERS
(2022)
Review
Cell Biology
Yohei Shinmyo, Toshihide Hamabe-Horiike, Kengo Saito, Hiroshi Kawasaki
Summary: The mammalian cerebral cortex has undergone significant changes during evolution, including an increase in size, the appearance of folds on its surface, and the complexity of neuronal circuits. However, the mechanisms underlying the development and evolution of the cerebral cortex are still not well understood. Recent advancements in genetic manipulation techniques using ferrets have provided a new approach to study these mechanisms. This review summarizes the recent findings regarding the development and evolution of the mammalian cerebral cortex, with a focus on research using ferrets.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Nicolas Cano-Astorga, Javier DeFelipe, Lidia Alonso-Nanclares
Summary: This study used FIB/SEM to investigate the synaptic organization in human tissue samples, revealing significant differences in synaptic density between autopsy and biopsy samples but a similar asymmetric:symmetric ratio. Synaptic junctions were primarily established on dendritic shafts and spines depending on their type.
Article
Psychiatry
Ling Hu, Bing-Yao Zhou, Cui-Ping Yang, Da-Yun Lu, Yun-Chao Tao, Lin Chen, Lei Zhang, Jun-Hui Su, Ying Huang, Ning-Ning Song, Jia-Yin Chen, Li Zhao, Yi Chen, Chun-Hui He, Yu-Bing Wang, Bing Lang, Yu-Qiang Ding
Summary: This study identifies a potential association between Ulk4 deficiency and schizophrenia, and demonstrates this association through experiments on mice. The study also finds that Ulk4 may regulate downstream signaling pathways through modulating GSK-3 signaling.
SCHIZOPHRENIA BULLETIN
(2022)
Article
Neurosciences
Nicolas Cano-Astorga, Sergio Plaza-Alonso, Javier DeFelipe, Lidia Alonso-Nanclares
Summary: The synaptic organization of the human anterior cingulate and temporopolar cortices was studied using FIB/SEM and revealed that Brodmann areas 24, 21, and ventral area 38 have similar synaptic density and size, whereas dorsal area 38 has the highest density and smallest size. However, the proportion and shapes of excitatory and inhibitory synapses were similar across all regions.
Article
Immunology
Zexi Yin, Xin Tian, Runying Zou, Xiangling He, Keke Chen, Chengguang Zhu
Summary: Activated phosphoinositide 3-kinase delta syndrome (APDS) is an autosomal dominant primary immunodeficiency caused by acquired gene function mutation, with clinical phenotypes such as recurrent respiratory infections and lymphoproliferation. Regular follow-up of APDS patients is recommended to prevent secondary tumors.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Neurosciences
Kanako Ishizuka, Hidenori Tabata, Hidenori Ito, Itaru Kushima, Mariko Noda, Akira Yoshimi, Masahide Usami, Kyota Watanabe, Mako Morikawa, Yota Uno, Takashi Okada, Daisuke Mori, Branko Aleksic, Norio Ozaki, Koh-ichi Nagata
JOURNAL OF NEUROSCIENCE RESEARCH
(2018)
Review
Biology
Hidenori Ito, Rika Morishita, Koh-ichi Nagata
MEDICAL MOLECULAR MORPHOLOGY
(2017)
Article
Cell Biology
Kyoko Ibaraki, Makoto Mizuno, Hitomi Aoki, Ayumi Niwa, Ikuko Iwamoto, Akira Hara, Hidenori Tabata, Hidenori Ito, Koh-ichi Nagata
ACTA HISTOCHEMICA ET CYTOCHEMICA
(2018)
Article
Neurosciences
Hidenori Ito, Makoto Mizuno, Kei Noguchi, Rika Morishita, Ikuko Iwamoto, Akira Hara, Koh-ichi Nagata
NEUROSCIENCE RESEARCH
(2018)
Article
Clinical Neurology
Nanako Hamada, Shunsuke Ogaya, Mitsuko Nakashima, Takuma Nishijo, Yuji Sugawara, Ikuko Iwamoto, Hidenori Ito, Yuki Maki, Kentaro Shirai, Shimpei Baba, Koichi Maruyama, Hirotomo Saitsu, Mitsuhiro Kato, Naomichi Matsumoto, Toshihiko Momiyama, Koh-ichi Nagata
Article
Developmental Biology
Hidenori Ito, Rika Morishita, Makoto Mizuno, Noriko Kawamura, Hidenori Tabata, Koh-ichi Nagata
DEVELOPMENTAL NEUROSCIENCE
(2018)
Review
Biochemistry & Molecular Biology
Hidenori Ito, Rika Morishita, Koh-ichi Nagata
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2018)
Article
Neurosciences
Hidenori Ito, Rika Morishita, Makoto Mizuno, Hidenori Tabata, Koh-ichi Nagata
Article
Genetics & Heredity
Kohji Kato, Fuyuki Miya, Nanako Hamada, Yutaka Negishi, Yoko Narumi-Kishimoto, Hiroshi Ozawa, Hidenori Ito, Ikumi Hori, Ayako Hattori, Nobuhiko Okamoto, Mitsuhiro Kato, Tatsuhiko Tsunoda, Yonehiro Kanemura, Kenjiro Kosaki, Yoshiyuki Takahashi, Koh-ichi Nagata, Shinji Saitoh
JOURNAL OF MEDICAL GENETICS
(2019)
Article
Multidisciplinary Sciences
Mariko Noda, Ikuko Iwamoto, Hidenori Tabata, Takanori Yamagata, Hidenori Ito, Koh-ichi Nagata
SCIENTIFIC REPORTS
(2019)
Article
Biology
Hidenori Ito, Rika Morishita, Mariko Noda, Ikuko Iwamoto, Koh-ichi Nagata
MEDICAL MOLECULAR MORPHOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Hidenori Ito, Rika Morishita, Mariko Noda, Tomoki Ishiguro, Masashi Nishikawa, Koh-ichi Nagata
Summary: CNKSR2 is a synaptic scaffolding molecule encoded by the CNKSR2 gene. The interaction with CYTH2 stabilizes a complex crucial for the proper development of dentate granule cells in the hippocampus. Knockdown of CNKSR2 or CYTH2 expression results in abnormal localization of cells and characteristics of immature granule cells.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Hidenori Ito, Koh-ichi Nagata
Summary: CNKSR2 is a scaffolding molecule that interacts with various molecules, playing a role in signal transduction and regulating neuronal development. It is considered as a causative gene for X-linked intellectual disability.
Article
Cell Biology
Masashi Nishikawa, Hidenori Ito, Hidenori Tabata, Hiroshi Ueda, Koh-ichi Nagata
Summary: The study found that the homozygosity of the p.Arg204Trp variation in the PLEKHG2 gene is responsible for microcephaly with intellectual disability. The function of PLEKHG2 during neurodevelopment was investigated using mouse models. The results suggest that PLEKHG2 is essential for the maturation of axons, dendrites, and spines, and impairment of its function may lead to neurodevelopmental disorders.
Article
Developmental Biology
Kyoko Ibaraki, Nanako Hamada, Ikuko Iwamoto, Hidenori Ito, Noriko Kawamura, Rika Morishita, Hidenori Tabata, Koh-ichi Nagata
DEVELOPMENTAL NEUROSCIENCE
(2019)