Article
Biochemistry & Molecular Biology
Thibault Courtellemont, Maria Giovanna De Leo, Navin Gopaldass, Andreas Mayer
Summary: Endo-lysosomal compartments exchange proteins through different processes, including fusion, fission, and endosomal transport carriers. The membrane fission events that occur during these processes are not well understood. This study identifies the CROP complex as a factor that plays a role in membrane fission. The CROP complex consists of members from two protein families and enhances the membrane fission activity of a specific protein. Disrupting the CROP complex prevents fragmentation of lysosome-like structures in yeast and impairs cargo export in mammalian endosomes.
Review
Cell Biology
Liriope Toupenet Marchesi, Marion Leblanc, Giovanni Stevanin
Summary: Hereditary spastic paraplegia (HSP) involves the degeneration of motor neurons and is characterized by clinical and genetic heterogeneity, making it challenging to find effective therapies. Several HSP genes/proteins are linked to the endolysosomal and autophagic pathways, suggesting a functional convergence, which may have implications for understanding the pathological mechanisms of HSP.
Review
Biochemistry & Molecular Biology
Katarzyna M. Grochowska, Maria Andres-Alonso, Anna Karpova, Michael R. Kreutz
Summary: Synaptic function relies on the constant supply and removal of neuronal membranes. Neuronal protein transport faces challenges due to the complexity of neurons, but local micro-secretory systems have evolved to meet the requirements of neuronal membrane protein proteostasis. However, our knowledge of neuronal protein synthesis, trafficking, replacement, and degradation is limited.
Article
Biochemistry & Molecular Biology
Elisabet Uribe-Carretero, Guadalupe Martinez-Chacon, Sokhna M. S. Yakhine-Diop, Gema Duque-Gonzalez, Mario Rodriguez-Arribas, Eva Alegre-Cortes, Marta Paredes-Barquero, Saray Canales-Cortes, Elisa Pizarro-Estrella, Antonio Cuadrado, Rosa Ana Gonzalez-Polo, Jose M. Fuentes, Mireia Niso-Santano
Summary: KEAP1 is an adaptor protein that plays an important role in regulating protein degradation. Loss of KEAP1 leads to protein oxidative aggregation and defective autophagy. Our study demonstrates that KEAP1 deficiency affects the endosome-lysosomal pathway, resulting in downregulation of cathepsin D and accumulation of autophagosomes.
Review
Cell Biology
Elena Gutierrez-Galindo, Zeynep Hazal Yilmaz, Angelika Hausser
Summary: Protein kinase D (PKD) is a serine/threonine kinase family that plays a crucial role in the secretory pathway at the trans-Golgi network. Abnormal expression of PKD isoforms is mainly found in breast cancer, where it promotes growth, invasion, survival, and stem cell maintenance. This review discusses the isoform-specific functions of PKD in breast cancer progression, specifically focusing on the connection between PKD-regulated cellular processes and deregulated membrane trafficking and secretion. The challenges of targeting PKD as a therapeutic approach to prevent breast cancer progression are also highlighted.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ying-Yue Yang, Wan-Li Wang, Xia-Tong Hu, Xin Chen, Yang Ni, Yan-Hua Lei, Qi-Yuan Qiu, Long-Yue Tao, Tian -Wen Luo, Ning-Yu Wang
Summary: The mammalian target of rapamycin (mTOR) has been proven to be an effective target for cancer therapy. Rapalogs and mTOR kinase inhibitors (TORKi) have been developed and clinically validated in several types of malignancies, with TORKi showing better antitumor activity by inhibiting both mTORC1 and mTORC2. However, the clinical development of current TORKi candidates has been relatively slow, and there is a need to develop more TORKi with novel scaffold to expand the current pipelines.
BIOORGANIC CHEMISTRY
(2023)
Article
Cell Biology
Eva Alegre-Cortes, Alberto Gimenez-Bejarano, Elisabet Uribe-Carretero, Marta Paredes-Barquero, Andre R. A. Marques, Mafalda Lopes-da-Silva, Otilia V. Vieira, Saray Canales-Cortes, Pedro J. Camello, Guadalupe Martinez-Chacon, Ana Aiastui, Roberto Fernandez-Torron, Adolfo Lopez de Munain, Patricia Gomez-Suaga, Mireia Niso-Santano, Rosa A. Gonzalez-Polo, Jose M. Fuentes, Sokhna M. S. Yakhine-Diop
Summary: Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase gene. Fibroblasts derived from DM1 patients show increased autophagy flux, enlarged endosomes, and lysosomes. The binding of EGF to EGFR and the internalization of EGFR are delayed in DM1 cells, but EGF-activated EGFR enhances the phosphorylation of AKT and ERK1/2.
Review
Biochemistry & Molecular Biology
Marijn Kuijpers, Domenico Azarnia Tehran, Volker Haucke, Tolga Soykan
Summary: Neurons present special challenges to the autophagy and endolysosomal systems due to their complex morphology and longevity. These systems play crucial roles in degrading defective proteins, maintaining cellular homeostasis, and participating in signaling in neurons, especially in axons.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Cell Biology
Sheikh Tahir Majeed, Asiya Batool, Rabiya Majeed, Nadiem Nazir Bhat, Muhammad Afzal Zargar, Khurshid Iqbal Andrabi
Summary: Phosphorylated S209-eIF4E interacts with the TOS motif of S6K1, releasing it from auto-inhibition and priming it for activation in an mTORC1-independent manner. The role of mTORC1 is limited to engaging eIF4E with the S6K1-TOS motif to influence S6K1's state of activation.
Article
Biochemistry & Molecular Biology
Julian Nuechel, Marina Tauber, Janica L. Nolte, Matthias Moergelin, Clara Tuerk, Beate Eckes, Constantinos Demetriades, Markus Plomann
Summary: This study identifies mTORC1 as a key regulator of GRASP55 localization in the Golgi through direct phosphorylation, revealing a physiological role for mTORC1 at this organelle. Inhibition of mTORC1 leads to dephosphorylation and relocalization of GRASP55. Multiple proteomic analyses show that many cargoes follow this unconventional secretory route to alter the cellular secretome and surfactome.
Review
Cell Biology
Suresh Kumar, Miguel Sanchez-alvarez, Fidel-Nicolas Lolo, Flavia Trionfetti, Raffaele Strippoli, Marco Cordani
Summary: Autophagy and the lysosomal system, known together as the autophagolysosomal system, play a crucial role in maintaining cellular health and homeostasis by clearing cellular waste. TFEB regulates this system by driving the expression of multiple genes, including components of the autophagolysosomal system. Reactive Oxygen Species (ROS) are key in the physiological and pathological roles of this system.
Article
Biochemistry & Molecular Biology
Amita Arora, Annukka M. Kivela, Ling Wang, Rimante Minkeviciene, Juuso H. Taskinen, Birong Zhang, Annika Koponen, Jing Sun, Michiko Shirane, You Zhou, Pirta Hotulainen, Camilla Raiborg, Vesa M. Olkkonen
Summary: During angiogenesis, Protrudin plays a key role in regulating angiogenic tube formation and promoting endothelial cell migration through its effects on FAK activation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Cell Biology
Wayne A. Cabral, Urraca L. Tavarez, Indeevar Beeram, Diana Yeritsyan, Yoseph D. Boku, Michael A. Eckhaus, Ara Nazarian, Michael R. Erdos, Francis S. Collins
Summary: Hutchinson-Gilford progeria syndrome (HGPS) is a rare accelerated aging disorder characterized by cardiovascular disease and premature death, mostly caused by a single nucleotide mutation in the LMNA gene. A study using mice models carrying two copies of the BAC showed a more complete replication of HGPS phenotypic features in various tissues, and genetic reduction of mTOR extended the lifespan of these mice significantly, suggesting a potential treatment for HGPS through pharmacologic inhibition of the mTOR pathway.
Article
Biochemistry & Molecular Biology
Kathryn J. Hattersley, Julian M. Carosi, Leanne K. Hein, Julien Bensalem, Timothy J. Sargeant
Summary: Disruption of the PICALM gene affects cellular degradative function, leading to an increase in early endosome numbers, abundance of lysosomal enzymes, and disruption to the processing and maturation of lysosomal protease, resulting in a deficit in autophagy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Cell Biology
Matias Blaustein, Estefania Piegari, Camila Martinez Calejman, Antonella Vila, Analia Amante, Maria Victoria Manese, Ari Zeida, Laurence Abrami, Mariela Veggetti, David A. Guertin, F. Gisou van der Goot, Maria Martha Corvi, Alejandro Colman-Lerner
Summary: The study reveals that Akt protein undergoes S-palmitoylation modification, affecting its localization and function. Lack of palmitoylation leads to increased recruitment of Akt to cytoplasmic structures co-localizing with lysosomes during autophagy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biology
Stephan A. Eisler, Filipa Curado, Gisela Link, Sarah Schulz, Melanie Noack, Maren Steinke, Monilola A. Olayioye, Angelika Hausser
Article
Biochemistry & Molecular Biology
Antje Jensch, Yannick Frey, Katharina Bitschar, Patrick Weber, Simone Schmid, Angelika Hausser, Monilola A. Olayioye, Nicole E. Radde
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Review
Biochemistry & Molecular Biology
Julia von Blume, Angelika Hausser
Review
Cell Biology
Monilola A. Olayioye, Bettina Noll, Angelika Hausser
Article
Gastroenterology & Hepatology
Shuya Zhang, Huan Liu, Meimei Yin, Xiuying Pei, Angelika Hausser, Eri Ishikawa, Sho Yamasaki, Zheng Gen Jin
Article
Oncology
Wolfgang S. Lieb, Cristiana Lungu, Raluca Tamas, Hannah Berreth, Philipp Rathert, Peter Storz, Monilola A. Olayioye, Angelika Hausser
INTERNATIONAL JOURNAL OF CANCER
(2020)
Article
Biochemistry & Molecular Biology
Ines Mueller, Elwira Strozyk, Sebastian Schindler, Stefan Beissert, Htoo Zarni Oo, Thomas Sauter, Philippe Lucarelli, Sebastian Raeth, Angelika Hausser, Nader Al Nakouzi, Ladan Fazli, Martin E. Gleave, He Liu, Hans-Uwe Simon, Henning Walczak, Douglas R. Green, Jiri Bartek, Mads Daugaard, Dagmar Kulms
Article
Cell Biology
Natalia Pacheco-Fernandez, Mehrshad Pakdel, Birgit Blank, Ismael Sanchez-Gonzalez, Kathrin Weber, Mai Ly Tran, Tobias Karl-Heinz Hecht, Renate Gautsch, Gisela Beck, Franck Perez, Angelika Hausser, Stefan Linder, Julia von Blume
JOURNAL OF CELL BIOLOGY
(2020)
Article
Cell Biology
Carlos O. Oueslati Morales, Attila Ignacz, Norbert Bencsik, Zsofia Sziber, Aniko Erika Ratkai, Wolfgang S. Lieb, Stephan A. Eisler, Attila Szucs, Katalin Schlett, Angelika Hausser
Summary: The PKD family promotes AMPAR endocytosis in primary hippocampal neurons, affecting synaptic plasticity. Inhibition of PKD increases AMPAR levels at synapses, slows down their endocytic trafficking, and enhances neuronal network activity. Conversely, ectopic expression of constitutive active PKD reduces synaptic AMPAR levels but increases their colocalization with early endosomes.
Article
Cell Biology
Cathrin Hagenlocher, Robin Siebert, Bruno Taschke, Senait Wieske, Angelika Hausser, Markus Rehm
Summary: Prolonged ER stress can trigger cell death, but the mechanism differs between cancer cells and pancreatic beta cells. This study found that ER stress-induced apoptosis in pancreatic beta cells does not involve TRAIL-R2, unlike in cancer cells. These findings have implications for targeted treatment strategies that need to consider the ER stress susceptibility of different cell types.
CELL DEATH DISCOVERY
(2022)
Article
Multidisciplinary Sciences
Ronja Reinhardt, Kai Hirzel, Gisela Link, Stephan A. Eisler, Tanja Hagele, Matthew A. H. Parson, John E. Burke, Angelika Hausser, Thomas A. Leonard
Summary: Phosphorylation is a common mechanism in cell signaling, and protein kinases are often regulated by phosphorylation. However, PKD regulates itself through dimerization-mediated trans-autoinhibition, followed by autophosphorylation, to control its activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Attila Ignacz, Domonkos Nagy-Herczeg, Angelika Hausser, Katalin Schlett
Summary: The actin cytoskeleton is the main regulator of synapse formation and maintenance. Different actin probes were compared in cultured hippocampal neurons to study their effectiveness in visualizing actin dynamics. The results showed that LifeAct-GFP and AC-GFP had similar affinity to actin, but they couldn't detect subtle changes in actin remodeling as effectively as EGFP-actin. Additionally, LifeAct-GFP had lower enrichment in dendritic spines compared to the other probes.
MOLECULAR BIOLOGY OF THE CELL
(2023)
Article
Oncology
Sophia Steinlein, Frank Essmann, Amanda Franceschini Ghilardi, Heike Horn, Julia Schueler, Angelika Hausser, Lijun Sun, German Ott, Claudia Kalla
Summary: In this study, two indolyl-chalcones (CIT-026 and CIT-223) were found to be highly effective in inhibiting the growth and viability of malignant pleural mesothelioma (MPM) cells, while having minimal effects on normal fibroblasts. These compounds induce tumor cell apoptosis by disrupting microtubule assembly and show promising potential as small-molecule therapeutics for MPM, especially in cells resistant to standard therapeutics.
FRONTIERS IN ONCOLOGY
(2023)
Review
Cell Biology
Elena Gutierrez-Galindo, Zeynep Hazal Yilmaz, Angelika Hausser
Summary: Protein kinase D (PKD) is a serine/threonine kinase family that plays a crucial role in the secretory pathway at the trans-Golgi network. Abnormal expression of PKD isoforms is mainly found in breast cancer, where it promotes growth, invasion, survival, and stem cell maintenance. This review discusses the isoform-specific functions of PKD in breast cancer progression, specifically focusing on the connection between PKD-regulated cellular processes and deregulated membrane trafficking and secretion. The challenges of targeting PKD as a therapeutic approach to prevent breast cancer progression are also highlighted.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Serena Capasso, Lucia Sticco, Riccardo Rizzo, Marinella Pirozzi, Domenico Russo, Nina A. Dathan, Felix Campelo, Josse van Galen, Maarit Holtta-Vuori, Gabriele Turacchio, Angelika Hausser, Vivek Malhotra, Isabelle Riezman, Howard Riezman, Elina Ikonen, Chiara Luberto, Seetharaman Parashuraman, Alberto Luini, Giovanni D'Angelo