Article
Chemistry, Physical
Andreas Santamaria, Javier Carrascosa-Tejedor, Eduardo Guzman, Nathan R. Zaccai, Armando Maestro
Summary: This study experimentally investigates the molecular organization of phosphatidylinositol 4,5-bisphosphate (PIP2) and reveals its correlation with the formation of transient PIP2 clusters in both lateral and perpendicular directions.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2023)
Article
Physiology
Junlan Zhou, Neha Singh, Chloe Monnier, William Marszalec, Li Gao, Jing Jin, Michael Frisk, William E. Louch, Suresh Verma, Prasanna Krishnamurthy, Elsa Nico, Maaz Mulla, Gary L. Aistrup, Raj Kishore, J. Andrew Wasserstrom
Summary: The study demonstrated that PIP2-mediated targeting of BIN1 to the sarcolemma may be compromised during heart failure development, leading to T-tubule remodeling. Additionally, the interaction between PIP2 and cardiac BIN1 is essential for T-tubule maintenance and function, with depletion of PIP2 potentially causing T-tubule disruption.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biology
Ana Bura, Antonija Jurak Begonja
Summary: Phosphoinositides play crucial roles in cells with limited understanding of their localization and functions in platelets. This study investigated the localization of PI(4,5)P-2 and PI4P in resting and activated platelets through antibody staining. The intracellular pools of PI(4,5)P-2 and PI4P in platelets can be modulated by inhibitors of OCRL phosphatase and PI4KIII alpha kinase, with a more sensitive response in activated platelets.
Review
Cell Biology
Ana Bura, Sara Cabrijan, Iris Duric, Tea Bruketa, Antonija Jurak Begonja
Summary: Phosphoinositides (PIs) are phosphorylated lipids that have diverse cellular functions including regulation of trafficking, actin reorganization, and cell signaling. The two most abundant PIs in cells are phosphatidylinositol4-monophosphate (PI4P) and phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], which localize to different cellular compartments and regulate various processes. The levels of PIs are controlled by multiple kinases and phosphatases, and understanding their localization and function is important for studying cellular processes.
Article
Cell Biology
Martin Sztacho, Barbora Salovska, Jakub Cervenka, Can Balaban, Peter Hoboth, Pavel Hozak
Summary: Analysis of nuclear protein interactions with phosphoinositides reveals the role of PIP2 in regulating gene expression, RNA splicing, and cell cycle processes. The identified proteins are involved in various functions within the nucleus, with different PIP2-binding motifs influencing their localization and activity. This study provides insights into the molecular mechanism of nuclear PIP2 protein interaction and offers a methodology for further research on PIPs and other protein ligands.
Article
Biochemistry & Molecular Biology
Leila Bechtella, Edward Chalouhi, Paula Milan Rodriguez, Marine Cosset, Delphine Ravault, Francoise Illien, Sandrine Sagan, Ludovic Carlier, Olivier Lequin, Patrick F. J. Fuchs, Emmanuelle Sachon, Astrid Walrant
Summary: In this study, the role of the negatively charged lipid phosphatidylinositol-4,5-bisphosphate (PI(4,5)P-2) in the internalization of Penetratin was analyzed. The results showed that Penetratin has a strong affinity for PI(4,S)P-2 and PI(4,5)P-2 plays an important role in Penetratin internalization.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biology
Katerina Cizkova, Katerina Koubova, Zdenek Tauber
Summary: This study revealed that activators and inhibitors of PPAR alpha affect the PI3K/Akt/PTEN pathway in intestinal cell differentiation, highlighting their impact on brush border formation.
Article
Biochemistry & Molecular Biology
Yong Shi, Anne Berking, Timo Baade, Kyle R. Legate, Reinhard Fassler, Christof R. Hauck
Summary: Staphylococcus aureus invades host cells mainly through an integrin-dependent manner, with phosphatidylinositol-4,5-bisphosphate (PI-4,5-P-2) playing a significant role in regulating integrin-associated proteins. Local synthesis of PI-4,5-P-2 by a focal adhesion-associated lipid kinase is crucial for integrin-mediated internalization of S. aureus. Targeting active PI-4,5-P-2 phosphatase to the plasma membrane and specific ablation of talin and FAK-binding motif in PIP5KI gamma 90 can reduce bacterial invasion.
MOLECULAR MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Bo-Hyun Lee, Jose J. De Jesus Perez, Vera Moiseenkova-Bell, Tibor Rohacs
Summary: Long-chain acyl-Coenzyme A (LC-CoA) is an important signaling molecule that activates TRPV5 and TRPV6 ion channels. The researchers discovered that LC-CoA and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) have the same mechanism in maintaining channel activity. By utilizing cryo-electron microscopy, the authors determined the structure of LC-CoA-bound TRPV5, providing insights into the regulation of ion channels by metabolic signaling molecules.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Yi Wen, Volker M. Vogt, Gerald W. Feigenson
Summary: Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) is a crucial component located at the inner leaflet of the cell membrane, constituting only 1-2% of total membrane lipids. Its synthesis and turnover are spatially and temporally regulated. Various factors, such as multivalent cations and cellular proteins interacting with PI(4,5)P-2, contribute to its versatile and dynamic distribution within membranes.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
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
Cell Biology
Liang Guo, Qionglei Mao, Ji He, Xiaoling Liu, Xuejiao Piao, Li Luo, Xiaoxu Hao, Hanzhi Yu, Qiang Song, Bailong Xiao, Dongsheng Fan, Zhaobing Gao, Yichang Jia
Summary: Rare variants of Chloride Channel CLIC Like 1 (CLCC1) are linked to amyotrophic lateral sclerosis (ALS)-like pathologies. CLCC1 is a pore-forming component of an endoplasmic reticulum (ER) anion channel, and ALS-associated mutations impair channel conductance. CLCC1 maintains ER ion homeostasis and regulates ER Ca2+ homeostasis, and disruption of this function contributes to ALS-like pathologies.
Article
Biochemistry & Molecular Biology
Maiwase Tembo, Rachel E. Bainbridge, Crystal Lara-Santos, Kayla M. Komondor, Grant J. Daskivich, Jacob D. Durrant, Joel C. Rosenbaum, Anne E. Carlson
Summary: This study investigates the interaction between TMEM16A channel and the membrane lipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2). The findings show that only lipids containing a phosphate at the 40 position effectively recover TMEM16A currents. These findings improve our understanding of how PI(4,5)P-2 binds to and potentiates TMEM16A channels.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biophysics
Thomas Ehret, Tim Heissenberg, Svenja de Buhr, Camilo Aponte-Santamaria, Claudia Steinem, Frauke Graeter
Summary: The four-point-one ezrin-radixin-moesin homology (FERM) protein domain is a multifunctional protein-lipid binding site, important for localization and activation of membrane-associated proteins. In contrast to static crystal structures, atomistic molecular dynamics simulations and experiments reveal higher stoichiometry of FERM-PIP2 binding, with ratios of 1:3 or 1:4, indicating a multi-valent binding of FERM domains to PIP2 in lipid bilayers.
BIOPHYSICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Hannah R. Ferris, Nathan C. Stine, David C. Hill-Eubanks, Mark T. Nelson, George C. Wellman, Masayo Koide
Summary: Functional hyperemia, which refers to the increase in local blood perfusion in response to enhanced neuronal activity, plays a crucial role in brain health. This study found that the impairment of endothelial epidermal growth factor receptor (EGFR) signaling resulted in crippled functional hyperemia, likely due to depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) and dysfunctional Kir2.1 channels in capillary endothelial cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Peter J. Huwe, Qifang Xu, Maxim V. Shapovalov, Vivek Modi, Mark D. Andrake, Roland L. Dunbrack
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2016)
Article
Oncology
Scott C. Bresler, Daniel A. Weiser, Peter J. Huwe, Jin H. Park, Kateryna Krytska, Hannah Ryles, Marci Laudenslager, Eric F. Rappaport, Andrew C. Wood, Patrick W. McGrady, Michael D. Hogarty, Wendy B. London, Ravi Radhakrishnan, Mark A. Lemmon, Yael P. Mosse
Article
Biochemistry & Molecular Biology
Kiran S. Gajula, Peter J. Huwe, Charlie Y. Mo, Daniel J. Crawford, James T. Stivers, Ravi Radhakrishnan, Rahul M. Kohli
NUCLEIC ACIDS RESEARCH
(2014)
Article
Oncology
Sanjeevani Arora, Peter J. Huwe, Rahmat Sikder, Manali Shah, Amanda J. Browne, Randy Lesh, Emmanuelle Nicolas, Sanat Deshpande, Michael J. Hall, Roland L. Dunbrack, Erica A. Golemis
CANCER BIOLOGY & THERAPY
(2017)