Article
Oncology
Suree Kim, Sukyeong Heo, Joseph Brzostowski, Dongmin Kang
Summary: This study focuses on the full activation of AKT, a key effector in PI3K-driven cell signal transduction, through phosphorylation at Thr308 and Ser473. It explores the mechanisms of AKT activation at early endosomes during growth factor stimulation, with a specific focus on the role of mTORC2 in this process. The research demonstrates the importance of endocytosis in AKT activation through mTORC2 phosphorylation at Ser473 and the involvement of endosomal phosphoinositide, PtdIns(3,4)P-2, in this signaling pathway.
Article
Biochemistry & Molecular Biology
Eniko Pergel, Iren Veres, Gergely Imre Csigi, Gabor Czirjak
Summary: TMEM175 coding sequence variants are associated with increased risk of Parkinson's disease, and its currents are significantly increased by the application of dynamin inhibitor compounds, suggesting dynamin-independent pharmacological effects may also contribute to the action on the channel. The data suggest that PKB-dependent regulation influences TMEM175 current in the plasma membrane.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Luther J. Davis, Nicholas A. Bright, James R. Edgar, Michael D. J. Parkinson, Lena Wartosch, Judith Mantell, Andrew A. Peden, J. Paul Luzio
Summary: Our study investigated the effects of SNAREs VAMP7 and VAMP8 knockout on late endocytic organelles' tethering and pore formation, as well as the role of CHMP6 depletion in filamentous tethering between multivesicular bodies and enlarged endolysosomes. The results show the accumulation of tethered lysosome-associated membrane protein (LAMP)-carrier vesicles and 'hourglass' profiles in the absence of VAMP7 and VAMP8, and provide evidence that pore formation starts at the edge of tether arrays, with pore expansion necessary for full membrane fusion.
JOURNAL OF CELL SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Yan Zhen, Maja Radulovic, Marina Vietri, Harald Stenmark
Summary: The compartmentalization of eukaryotic cells is essential for their viability, with membranes forming boundaries between organelles and the cytosol. Cellular membranes can be compromised by various factors, but there are evolved mechanisms like membrane scission and endocytosis to maintain membrane integrity.
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
Biology
Junko Y. Toshima, Ayana Tsukahara, Makoto Nagano, Takuro Tojima, Daria E. Siekhaus, Akihiko Nakano, Jiro Toshima, Sean Munro
Summary: Budding yeast possesses an independent endocytic early/sorting compartment within the trans-Golgi network (TGN) that sorts endocytic cargos. This compartment functions as the target for endocytic vesicles and is involved in recycling to the plasma membrane or transport to the Rab5 endosomal compartment. The Tlg2p protein, a homolog of yeast syntaxin, resides in this compartment and acts as a Q-SNARE for endocytic vesicles.
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
Multidisciplinary Sciences
Shota Shimizu, Kazuaki Yoshioka, Sho Aki, Yoh Takuwa
Summary: PI3K-C2 alpha is essential for clathrin-mediated endocytosis of the gamma-secretase complex, facilitating the cleavage of endocytosed Notch1 by the gamma-secretase complex to generate NICD1 in ECs.
SCIENTIFIC REPORTS
(2021)
Review
Genetics & Heredity
Chung-Ling Lu, Jinoh Kim
Summary: Cells utilize membrane-bound carriers to transport signaling molecules to their destinations, and variations in the genes encoding intracellular trafficking machinery can lead to craniofacial diseases. Despite the fundamental importance of trafficking pathways in craniofacial morphogenesis, there has been relatively less emphasis on this topic so far.
Review
Neurosciences
Daniela Ivanova, Michael A. Cousin
Summary: The endolysosomal system plays a crucial role in cells and inter-neuronal communication. It has been found that molecules involved in endolysosomal function are also important for the recycling of neurotransmitter-containing synaptic vesicles. Therefore, a rethinking of the understanding of membrane trafficking at the presynapse is proposed.
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2022)
Article
Biochemical Research Methods
Amy Ryan, Gerald R. V. Hammond, Alexander Deiters
Summary: The study introduces a highly efficient method for optical control of protein localization through site-specific incorporation of a photocaged amino acid. It has been shown to be applicable to different proteins and can rapidly activate cellular signaling pathways.
ACS SYNTHETIC BIOLOGY
(2021)
Article
Chemistry, Analytical
Mei C. Q. Houser, Shane P. C. Mitchell, Priyanka Sinha, Brianna Lundin, Oksana Berezovska, Masato Maesako
Summary: Our previous studies using FRET biosensors have shown that gamma-secretase primarily processes APP C99 in late endosomes and lysosomes in live neurons. In this study, we demonstrate that the endo-lysosomal membrane in primary neurons is more disordered and permeable compared to CHO cells. We also find that gamma-secretase has decreased processivity in primary neurons, resulting in the production of longer A beta 42 peptides. These findings support the functional interaction between lipid membrane properties and gamma-secretase in live cells.
Article
Oncology
Chenyang Qi, Liping Zou, Suxia Wang, Xing Mao, Yuan Hu, Jiaoyu Shi, Zhigang Zhang, Huijuan Wu
Summary: This study reveals that Vps34 acts as an invasion suppressor in hepatocellular carcinoma (HCC) cells. Vps34 can promote lysosomal juxtanuclear accumulation, leading to a reduction in HCC cell invasion through the Rab7-RILP pathway. Additionally, the deficiency of Vps34 in HCC cells affects the endosome-lysosome system, resulting in enhanced Rab11-mediated endocytic recycling of cell surface receptors and increased HCC cell invasion.
CANCER RESEARCH AND TREATMENT
(2022)
Article
Clinical Neurology
Alexander Svanbergsson, Fredrik Ek, Isak Martinsson, Jordi Rodo, Di Liu, Edoardo Brandi, Caroline Haikal, Laura Torres-Garcia, Wen Li, Gunnar Gouras, Roger Olsson, Tomas Bjorklund, Jia-Yi Li
Summary: This study identified inhibitors capable of preventing α-synuclein aggregation by targeting p38 MAPK and PKC, suggesting their potential therapeutic value. The research also revealed alterations in the endo-lysosomal system as likely candidates for the protective effects, underscoring the importance of high-throughput screening in investigating α-synuclein aggregation mechanisms and discovering novel therapeutic compounds.
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
Oncology
L. Sun, Y. Shi, G. Wang, X. Wang, S. Zeng, S. E. Dunn, G. D. Fairn, Y-J Li, D. E. Spaner
Article
Biochemistry & Molecular Biology
Minhyoung Lee, Gregory D. Fairn
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2018)
Review
Biochemistry & Molecular Biology
Stella M. Lu, Gregory D. Fairn
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2018)
Article
Cell Biology
Mira Sohn, Marek Korzeniowski, James P. Zewe, Rachel C. Wills, Gerald R. V. Hammond, Jana Humpolickova, Lukas Vrzal, Dominika Chalupska, Vaclav Veverka, Gregory D. Fairn, Evzen Boura, Tamas Balla
JOURNAL OF CELL BIOLOGY
(2018)
Article
Cell Biology
Stella M. Lu, Gregory D. Fairn
Editorial Material
Biology
Kevin C. Courtney, Karen Y. Y. Fung, Frederick R. Maxfield, Gregory D. Fairn, Xiaohui Zha
Article
Microbiology
Joel M. J. Tan, Nora Mellouk, Suzanne E. Osborne, Dustin A. Ammendolia, Diana N. Dyer, Ren Li, Diede Brunen, Jorik M. van Rijn, Ju Huang, Mark A. Czuczman, Marija A. Cemma, Amy M. Wons, Christopher M. Yip, Ramnik J. Xavier, Donna A. MacDuff, Fulvio Reggiori, Jayanta Debnath, Tamotsu Yoshimori, Peter K. Kim, Gregory D. Fairn, Etienne Coyaud, Brian Raught, Aleixo M. Muise, Darren E. Higgins, John H. Brumell
NATURE MICROBIOLOGY
(2018)
Article
Physiology
Hira Raheel, Siavash Ghaffari, Negar Khosraviani, Victoria Mintsopoulos, Derek Auyeung, Changsen Wang, Yun Hye Kim, Brendan Mullen, Hoon-Ki Sung, May Ho, Gregory Fairn, Dante Neculai, Maria Febbraio, Bryan Heit, Warren L. Lee
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2019)
Review
Cell Biology
Johannes Westman, Bernhard Hube, Gregory D. Fairn
CELLULAR MICROBIOLOGY
(2019)
Article
Cell Biology
Philip P. Ostrowski, Spencer A. Freeman, Gregory Fairn, Sergio Grinstein
DEVELOPMENTAL CELL
(2019)
Article
Multidisciplinary Sciences
Yanbo Yang, Miriam Park, Masashi Maekawa, Gregory D. Fairn
SCIENTIFIC REPORTS
(2019)
Article
Cell Biology
Fernando Montano-Rendon, Glenn F. W. Walpole, Matthias Krause, Gerald R. V. Hammond, Sergio Grinstein, Gregory D. Fairn
Summary: PI 3-kinase is crucial for phagocytosis, with PI3,4P2, Lamellipodin, and VASP playing essential roles in actin-driven pseudopod extension and particle engulfment. Phosphoinositides are key regulators of vesicular traffic and signaling during phagocytosis, with locally generated PtdIns(3,4)P-2 influencing pseudopod progression and phagocytosis. Lamellipodin and VASP are important actin-regulatory proteins involved in phagosome formation downstream of PtdIns(3,4)P-2.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Cell Biology
John Abousawan, Laura A. Orofiamma, Gregory D. Fairn, Costin N. Antonescu
Summary: The epidermal growth factor receptor (EGFR) controls many cellular functions by undergoing dimerization, phosphorylation, and activation of signals including the PI3K-Akt pathway upon ligand binding. The role of flotillin nanodomains in EGFR signaling remains unclear, as some studies suggest their involvement while others show limited effect. This study reveals that HER2 expression alters EGFR signaling duration and requires flotillin-1 and c-Src for Akt activation and cell proliferation.
JOURNAL OF CELL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Michael G. Sugiyama, Aidan I. Brown, Jesus Vega-Lugo, Jazlyn P. Borges, Andrew M. Scott, Khuloud Jaqaman, Gregory D. Fairn, Costin N. Antonescu
Summary: Using single particle tracking, the authors discovered that EGFR is more confined when bound to ligands, and this confinement is regulated by clathrin and tetraspanin nanodomains. Ligand binding to unliganded EGFR occurs mainly in tetraspanin nanodomains, and disrupting these nanodomains impairs ligand binding and alters the receptor's ectodomain conformation. This study reveals a mechanism by which EGFR confinement within tetraspanin nanodomains regulates ligand binding and signaling.
NATURE COMMUNICATIONS
(2023)