Article
Multidisciplinary Sciences
Nilmani Singh, Adriana Reyes-Ordonez, Michael A. Compagnone, Jesus F. Moreno Castillo, Benjamin J. Leslie, Taekjip Ha, Jie Chen
Summary: This study explores the specific interactions of human PH domain-containing proteins with PIPs and reveals unexpected lipid-binding specificity among these proteins. By analyzing the structural requirements and functional relevance of PIP binding, as well as using a prediction algorithm, the researchers demonstrate widespread PIP binding among human PH domains.
NATURE COMMUNICATIONS
(2021)
Article
Biochemical Research Methods
Michelle Palmieri, Bruno Catimel, Dmitri Mouradov, Anuratha Sakthianandeswaren, Eugene Kapp, Ching-Seng Ang, Nicholas A. Williamson, Cameron J. Nowell, Michael Christie, Jayesh Desai, Peter Gibbs, Antony W. Burgess, Oliver M. Sieber
Summary: The nuclear translocation of PI3K alpha regulates the subcellular levels of PtdIns(3,4,5)P3 in colorectal cancer cell lines, and 867 potential nuclear PtdIns(3,4,5)P3 effector proteins have been identified. These effector proteins are mainly involved in RNA metabolism and may play a role in modulating pre-mRNA splicing. These findings suggest that nuclear PI3K alpha signaling through PtdIns(3,4,5)P3 effector proteins is important for CRC development.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Plant Sciences
Gwennogan A. Dubois, Yvon Jaillais
Summary: Anionic phospholipids, such as phosphatidic acid and phosphatidylserine, are low-abundant lipids that play important roles in membrane functions. They accumulate in different endomembranes according to unique subcellular patterns and form concentration gradients across organelles, challenging the initial belief in their compartment-specificity.
Article
Multidisciplinary Sciences
Dhanushan Wijayaratna, Kasun Ratnayake, Sithurandi Ubeysinghe, Dinesh Kankanamge, Mithila Tennakoon, Ajith Karunarathne
Summary: Phosphatidylinositol (3,4,5) trisphosphate (PIP3) is a plasma membrane-bound signaling phospholipid involved in various cellular processes, and defective PIP3 signaling is implicated in several diseases. Our data show that G protein subcellular redistributions regulate the attenuation of PIP3 when GPCRs are activated, with different effects depending on Gγ subtypes. These findings demonstrate the regulation of GPCR-induced PIP3 response and the diversity of cell responses to spatial and temporal variability of external stimuli.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Giulia Unali, Giovanni Crivicich, Isabel Pagani, Monah Abou-Alezz, Filippo Folchini, Erika Valeri, Vittoria Matafora, Julie A. Reisz, Anna Maria Sole Giordano, Ivan Cuccovillo, Giacomo M. Butta, Lorena Donnici, Angelo D'Alessandro, Raffaele De Francesco, Lara Manganaro, Davide Cittaro, Ivan Merelli, Carolina Petrillo, Angela Bachi, Elisa Vicenzi, Anna Kajaste-Rudnitski
Summary: The interferon-induced transmembrane proteins (IFITM) inhibit endocytic viral entry by binding to phosphatidylinositol 3,4,5-trisphosphate (PIP3), which plays a key role in endosomal antiviral immunity. The level of PIP3 is closely correlated with the potency of endosomal IFITM restriction, and exogenous PIP3 enhances the inhibition of endocytic viruses. These findings elucidate cell-compartment-specific antiviral mechanisms and have potential relevance for the development of broadly acting antiviral strategies.
Article
Biochemistry & Molecular Biology
Nina Nelson, Adelia Razeto, Alessia Gilardi, Mira Graettinger, Johannes Kirchmair, Manfred Juecker
Summary: Phosphoinositides PtdIns(3,4,5)P-3 and PtdIns(3,4)P-2 act as second messengers in cancerogenesis, with their downstream signaling mediated through a complex network of phosphoinositide binding effector proteins and phosphatases. Experimental results demonstrate high affinity phosphoinositide binding for most proteins tested, with AKT1 showing the highest affinity among effector proteins and PTEN displaying the highest affinity among phosphatases.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Neurosciences
Yoshibumi Ueda, Naotoshi Sugimoto, Takeaki Ozawa
Summary: This study revealed the accumulation of PIP3 in dendritic spines during neuronal development and its strict control in an active state. These findings deepen our understanding of PIP3 dynamics in dendritic spines and suggest a potential link between dysregulation of the PIP3 gradient and neuronal diseases and mental disorders.
Article
Biochemical Research Methods
Fatemeh Mazloumi Gavgani, Malene Skuseth Slinning, Andrea Papdine Morovicz, Victoria Smith Arnesen, Diana C. Turcu, Sandra Ninzima, Clive S. D'Santos, Aurelia E. Lewis
Summary: Polyphosphoinositides (PPIns) are essential lipid signaling molecules with functions in both cytoplasm and nucleus. This study identified 179 potential interacting partners of PtdIns(3,4,5)P-3 in the isolated nuclei, revealing their roles in RNA processing/splicing, cytokinesis, protein folding, and DNA repair. Notably, some of the interacting proteins have dual functions in rRNA processes and DNA repair, providing insights into the molecular mechanisms of PtdIns(3,4,5)P-3-mediated interactions in the nucleus and nucleolus.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Clinical Neurology
Chi-Jing Choong, Cesar Aguirre, Keita Kakuda, Goichi Beck, Hiroki Nakanishi, Yasuyoshi Kimura, Shuichi Shimma, Kei Nabekura, Makoto Hideshima, Junko Doi, Keiichi Yamaguchi, Kichitaro Nakajima, Tomoya Wadayama, Hideki Hayakawa, Kousuke Baba, Kotaro Ogawa, Toshihide Takeuchi, Shaymaa Mohamed Mohamed Badawy, Shigeo Murayama, Seiichi Nagano, Yuji Goto, Yohei Miyanoiri, Yoshitaka Nagai, Hideki Mochizuki, Kensuke Ikenaka
Summary: The functional loss of SYNJ1 leads to elevated levels of PIP3, which promotes the pathological aggregation of alpha Syn and increases the risk of developing Parkinson's disease. This relationship was confirmed through cellular and model organism experiments, as well as analysis of postmortem brain samples from PD patients. These findings suggest that PIP3 may be a promising target for interventions in Parkinson's disease.
ACTA NEUROPATHOLOGICA
(2023)
Article
Biophysics
Jackson Weako, Hyunbum Jang, Ozlem Keskin, Ruth Nussinov, Attila Gursoy
Summary: This study investigates the atomic-level interaction between CaM and Akt's PHD through modeling and molecular dynamics simulations, showing that the interaction is thermodynamically stable and involves a beta-strand instead of an alpha-helix. The polar head of PIP3 weakens the CaM-PHD interaction, suggesting a release mechanism at the plasma membrane.
BIOPHYSICAL JOURNAL
(2021)
Review
Cell Biology
Junya Hasegawa, Yasunori Uchida, Kojiro Mukai, Shoken Lee, Tatsuyuki Matsudaira, Tomohiko Taguchi
Summary: Cells internalize proteins and lipids through endocytosis, maintaining a balance in the plasma membrane by replenishing through a recycling pathway. In addition to their role in recycling, recycling endosomes have been found to play unexpected roles in membrane traffic and cell signaling. This review highlights these emerging issues, particularly focusing on phosphatidylserine and the pathogenesis of Hermansky Pudlak syndrome type 2 related to dysregulated recycling endosome functions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Madeline R. Sponholtz, Eric N. Senning
Summary: Using total internal reflection fluorescence microscopy, we observed the dissociation of GFP-tagged pleckstrin homology (PH) domains of AKT and PLC delta 1 from the plasma membranes of cells, and found that substantial rebinding events occurred in PLC delta 1-PH-GFP dissociation kinetics. By applying inositol triphosphate (IP3) during the unroofing process, we suppressed rebinding events significantly, indicating competitive action between IP3 and phosphatidylinositol 4,5-bisphosphate (PIP2) for the same binding site. Our discussion revolves around how free PIP2 levels modulate the interaction between membrane-associated proteins and the plasma membrane.
ACS CHEMICAL NEUROSCIENCE
(2021)
Editorial Material
Cell Biology
Rodrigo Enrique Gomez, Julie Castets, Josselin Lupette, Clement Chambaud, Jerome Joubes, Amelie Bernard
Summary: Autophagy is a key mechanism in plants that helps them adapt to various environmental constraints. The molecular mechanisms, especially autophagosome formation, remain poorly understood. A recent study used biochemistry, genetics, cell biology, and high-resolution 3D imaging to uncover the function of lipid phosphatidylinositol-4-phosphate (PtdIns4P) in autophagy in Arabidopsis thaliana, providing new insights into autophagosome assembly in plant cells.
Article
Multidisciplinary Sciences
Veronika Thallmair, Lea Schultz, Wencai Zhao, Siewert J. Marrink, Dominik Oliver, Sebastian Thallmair
Summary: Phosphoinositides (PIs), especially phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2], play a crucial role in targeting proteins to cilia. This study discovered that the tubby domain, which is essential for this targeting process, binds to PI(4,5)P-2 through two binding sites.
Article
Medicine, General & Internal
Alaaeldin G. Fayez, Nora N. Esmaiel, Engy A. Ashaat, Miral M. Refeat, Randa S. Lotfy, Haiam Abdel Raouf, Mona O. El Ruby
Summary: This study aimed to validate the Vars2-Pic3ca-Akt pathway, which has been hypothesized to be associated with CTDs, through experimental measurements of Vars2 and PIP3 in CTD patients and the development of a PIP3 inhibitor. The results confirmed that CTD pathogenesis is related to Vars2-Pic3ca-Akt overstimulation and identified a new molecule, 322PESB, that antagonizes PIP3 binding. The Akt-pharmacophore feature model was used for discovery of PIP3 signaling antagonists.
JOURNAL OF TAIBAH UNIVERSITY MEDICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)