Article
Biochemistry & Molecular Biology
Agata Gluszek-Kustusz, Benjamin Craske, Thibault Legal, Toni McHugh, Julie P. Welburn
Summary: During mitosis, the microtubule crosslinker protein PRC1 recruits motor proteins CENP-E and Kif4A to the central spindle to coordinate chromosome segregation and cytokinesis. This recruitment is mediated by a conserved hydrophobic motif and is spatially and temporally regulated by CENP-E. The interaction between PRC1 and microtubule motor proteins is essential for controlling chromosome partitioning, maintaining central spindle integrity, and ensuring cytokinesis during anaphase.
Editorial Material
Clinical Neurology
Eduardo Benarroch
Summary: Stathmin-2, regulated by nuclear TDP-43, plays a crucial role in axonal development and repair. Reduced nuclear TDP-43 function leads to improper splicing of the gene encoding STMN2, resulting in the production of a truncated protein which is linked to axonal degeneration.
Article
Oncology
Michael Guenther, Sai Agash Surendran, Michael Haas, Volker Heinemann, Michael von Bergwelt-Baildon, Jutta Engel, Jens Werner, Stefan Boeck, Steffen Ormanns
Summary: This study found that high TPX2 expression is associated with increased malignancy in PDAC and gemcitabine resistance. It suggests that high TPX2 expression can serve as a negative predictor of gemcitabine-based palliative and adjuvant chemotherapy in PDAC, providing valuable information for clinical therapy decisions.
BRITISH JOURNAL OF CANCER
(2023)
Article
Cell Biology
Christine W. Bruggeman, Guus H. Haasnoot, Noemie Danne, Jaap van Krugten, Erwin J. G. Peterman
Summary: Cilia are membrane-enveloped organelles protruding from cell surfaces, crucial for sensing external environment. Chemical stimulation causes changes in ciliary structure and intra-flagellar transport, leading to different neuronal activity responses. The findings suggest cilia can sense and respond to external cues in distinct ways, highlighting their flexible nature as sensing hubs.
Review
Endocrinology & Metabolism
Ruben Nogueiras, Guadalupe Sabio
Summary: The article highlights the role of hypothalamic stress induced by nutrient overload as a major contributor to obesity and related diseases, with a particular focus on the importance of the JNK kinases in the brain. Recent research suggests opposing roles for JNK1 and JNK3 in AgRP neurons of the hypothalamus, demonstrating the complexity of JNK biology.
Article
Neurosciences
Fantao Meng, Jing Liu, Juanjuan Dai, Haifeng Lian, Shujun Jiang, Qiongyu Li, Min Wu, Wentao Wang, Dan Wang, Di Zhao, Cuilan Liu, Changyun Qiu, Chen Li
Summary: This study revealed that PPM1F may regulate anxiety-related behaviors by modulating BDNF expression and H3S10 phosphorylation-mediated epigenetic modification, serving as potentially pathological genes associated with anxiety or other mental diseases.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Cell Biology
Lang Shi, Hongchu Zha, Zhou Pan, Jiayi Wang, Yao Xia, Huimin Li, Hua Huang, Ruchi Yue, Zhixia Song, Jiefu Zhu
Summary: The study suggests that DUSP1 plays a critical role in maintaining mitochondrial function and structural integrity. DUSP1 protects against AKI by preventing BAX-induced mtDNA leakage and blocking excessive activation of the cGAS-STING signaling axis through JNK dephosphorylation.
CELL DEATH & DISEASE
(2023)
Review
Cell Biology
Rupkatha Banerjee, Shermali Gunawardena
Summary: It has been 25 years since the discovery of phosphorylation in molecular motors, but the specific contribution of kinases to motor functions, particularly in vivo, and the evolutionary conservation of these processes, still remain largely unanswered. There is a critical need to understand how kinases regulate molecular motors due to their crucial role in intracellular processes and cell viability, as disruptions can lead to diseases such as cancer and neurodegeneration. This review focuses on the role of phosphorylation in controlling kinesin-1 motility and presents evidence for a novel regulatory mechanism involving the kinase glycogen synthase kinase 3 beta (GSK3 beta) and the scaffolding protein presenilin (PS).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Diksha Kumari, Krishanu Ray
Summary: Phosphorylation of Kinesin subunits and adaptors plays a crucial role in regulating the activity and interactions of Kinesin motors, influencing intracellular transport dynamics.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Salma M. M. Eraky, Dalia H. H. El-Kashef, Mohamed El-Sherbiny, Nada F. Abo F. El-Magd
Summary: This study investigated the prophylactic impact of naringenin on thioacetamide-induced hepatic encephalopathy. The results showed that naringenin effectively mitigated TAA-induced behavioral, structural, and functional alterations, as well as cognitive impairment. Furthermore, naringenin reduced the levels of liver and cerebral JNK and SORT1, and elevated the levels of pro-BDNF and BDNF.
Article
Psychiatry
Bangkun Yang, Lesheng Wang, Ying Nie, Wei Wei, Wenping Xiong
Summary: The study revealed that proBDNF plays a significant role in the pathophysiology of PSD, affecting cellular apoptosis and depression-related proteins. The mechanism may involve the promotion of cellular apoptosis and the inhibition of nerve synapse regeneration by proBDNF, contributing to the progression of PSD.
TRANSLATIONAL PSYCHIATRY
(2021)
Article
Plant Sciences
Suneet Mehrotra, Marsha L. Pierce, Zhengyu Cao, Sairam Jabba, William H. Gerwick, Thomas F. Murray
Summary: Voltage-gated sodium channel (VGSC) activators like ATX promote neurite outgrowth by increasing intracellular Na+ concentration and upregulating NMDAR function. ATX enhances the synthesis and release of BDNF and enhances neurite outgrowth through the NMDAR-BDNF-TrkB-dependent mechanism.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Neurosciences
Irune Guerra San Juan, Leslie A. Nash, Kevin S. Smith, Marcel F. Leyton-Jaimes, Menglu Qian, Joseph R. Klim, Francesco Limone, Alexander B. Dorr, Alexander Couto, Greta Pintacuda, Brian J. Joseph, D. Eric Whisenant, Caroline Noble, Veronika Melnik, Deirdre Potter, Amie Holmes, Aaron Burberry, Matthijs Verhage, Kevin Eggan
Summary: This study found that disrupting a single TDP43-regulated RNA gene is sufficient to cause substantial motor dysfunction, indicating that disruption of TDP43 function likely contributes to ALS.
Article
Biochemistry & Molecular Biology
Jinrun Zhou, Yujuan Yao, Jiaojiao Zhang, Zhaohui Wang, Tianshu Zheng, Yao Lu, Weihua Kong, Jing Zhao
Summary: Myocardial apoptosis induced by myocardial ischemia and hyperlipemia are the main causes of high mortality of cardiovascular diseases. This study found that early growth response protein 1 (EGR-1) is involved in both types of apoptosis and identified the mechanism of EGR-1 entering the nucleus.
Article
Cell Biology
Jessica J. A. Hummel, Casper C. Hoogenraad
Summary: The study introduces an engineered kinesin motor toolbox for exploring the selectivity and regulatory mechanisms of intracellular cargo transport. Systematic screening of different kinesin tails and neuronal vesicles can address the selectivity of cargo-motor interaction, and the toolbox allows for investigation of regulatory mechanisms of kinesin-cargo interactions, such as the PX domain regulation of cargo trafficking by KIF16B.
JOURNAL OF CELL SCIENCE
(2021)
Article
Cell Biology
Eitan Erez Zahavi, Jessica J. A. Hummel, Yuhao Han, Citlali Bar, Riccardo Stucchi, Maarten Altelaar, Casper C. Hoogenraad
Summary: The study found that newly synthesized TrkB receptors are delivered directly into axons through the secretory pathway and are regulated by Rab6. The combined activity of kinesin-1 and kinesin-3 is essential for the formation of axon-bound TrkB secretory carriers and their efficient anterograde transport along the axon.
DEVELOPMENTAL CELL
(2021)
Correction
Cell Biology
Eitan Erez Zahavi, Jessica J. A. Hummel, Yuhao Han, Citlali Bar, Riccardo Stucchi, Maarten Altelaar, Casper C. Hoogenraad
DEVELOPMENTAL CELL
(2021)
Article
Biochemistry & Molecular Biology
Feline W. Lindhout, Sybren Portegies, Robbelien Kooistra, Lotte J. Herstel, Riccardo Stucchi, Jessica J. A. Hummel, Nicky Scheefhals, Eugene A. Katrukha, Maarten Altelaar, Harold D. MacGillavry, Corette J. Wierenga, Casper C. Hoogenraad
Summary: Centrosomes play a crucial role in controlling axon formation in human iPSC-derived neurons, as depletion of centrioles results in various axon developmental defects. Loss of centrioles affects axonal microtubule reorganization, which is essential for proper axon development and function. Live-cell imaging reveals the impaired microtubule dynamics in axons lacking centrioles during early development.
Article
Neurosciences
Eitan Erez Zahavi, Casper C. Hoogenraad
Summary: Nerve axons, shaped like long electric wires, transmit information quickly. A well-organized trafficking network is needed to transport cellular cargos from neuronal cell bodies to distal processes. In addition to motor proteins, subcellular membrane specializations and microtubule modifications play crucial roles in regulating cargo transport along the axon.
CURRENT OPINION IN NEUROBIOLOGY
(2021)
Article
Cell Biology
Jessica J. A. Hummel, Casper C. Hoogenraad
Summary: In this study, the authors systematically investigated the selectivity and regulation of KIF1A-driven transport of different types of vesicles, emphasizing the importance of phosphorylation for vesicle binding and the role of specific adaptors in achieving cargo specificity. They propose a model where motor dimerization, posttranslational modifications, and specific adaptors regulate selective KIF1A cargo trafficking.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Jessica J. A. Hummel, Casper C. Hoogenraad
Summary: The study introduces an engineered kinesin motor toolbox for exploring the selectivity and regulatory mechanisms of intracellular cargo transport. Systematic screening of different kinesin tails and neuronal vesicles can address the selectivity of cargo-motor interaction, and the toolbox allows for investigation of regulatory mechanisms of kinesin-cargo interactions, such as the PX domain regulation of cargo trafficking by KIF16B.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemical Research Methods
Ye Hong, Dani Flinkman, Tomi Suomi, Sami Pietila, Peter James, Eleanor Coffey, Laura L. Elo
Summary: This article introduces an integrated pipeline that utilizes multiple R packages to extract high-level biological understanding from large-scale phosphoproteomic data. The pipeline includes data clean-up, statistical analysis, differential expression analysis, phosphosite annotation and translation, enrichment analysis, proteome-wide kinase activity and substrate mapping, and network hub analysis.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Cell Biology
Ivar Noordstra, Cyntha M. van den Berg, Fransje W. J. Boot, Eugene A. Katrukha, Ka Lou Yu, Roderick P. Tas, Sybren Portegies, Bastiaan J. Viergever, Esther de Graaff, Casper C. Hoogenraad, Eelco J. P. de Koning, Francoise Carlotti, Lukas C. Kapitein, Anna Akhmanova
Summary: Insulin secretion in pancreatic beta-cells is regulated by cortical complexes that are enriched at the sites of adhesion to the extracellular matrix. Non-neuronal proteins LL5 beta and KANK1 are also present at insulin secretion sites and are involved in organizing exocytotic machinery. The dynamics of ELKS, an essential component of secretory complexes, is driven by binding and unbinding to low-mobility scaffolds, which are stimulated by glucose treatment. This study provides insights into the spatial organization of glucose-stimulated insulin release.
JOURNAL OF CELL SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Apoorva Sarode, Yuchen Fan, Amy E. Byrnes, Michal Hammel, Greg L. Hura, Yige Fu, Ponien Kou, Chloe Hu, Flora Hinz, Jasmine Roberts, Stefan G. Koenig, Karthik Nagapudi, Casper C. Hoogenraad, Tao Chen, Dennis Leung, Chun-Wan Yen
Summary: Lipid nanoparticles (LNPs) have gained attention in nucleic acid delivery field due to the success of mRNA COVID-19 vaccines. PEGylated lipids (PEG-lipids) as one of the constituent lipids on LNP surfaces play a crucial role in defining LNP properties. Research suggests that tuning PEG-lipid parameters can modulate LNP performance. To fully understand LNP behavior, a high-throughput screening (HTS) workflow was developed to prepare, characterize, and assess LNPs loaded with therapeutic antisense oligonucleotide (ASO).
NANOSCALE ADVANCES
(2022)
Correction
Biochemical Research Methods
Ye Hong, Dani Flinkman, Tomi Suomi, Sami Pietila, Peter James, Eleanor Coffey, Laura L. Elo
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Elena Tortosa, Arundhati Sengupta Ghosh, Qingling Li, Weng Ruh Wong, Trent Hinkle, Wendy Sandoval, Christopher M. Rose, Casper C. Hoogenraad
Summary: The phosphorylation and membrane localization of DLK, a component of MAPK, is crucial for its activation during neuronal stress responses. The recruitment of DLK to specific vesicles upon stress induces kinase activation, which is essential for neuronal survival and degeneration.
Article
Biochemistry & Molecular Biology
Giulia Montagna, Giuseppe Pani, Dani Flinkman, Francesco Cristofaro, Barbara Pascucci, Luca Massimino, Luigi Antonio Lamparelli, Lorenzo Fassina, Peter James, Eleanor Coffey, Giuseppina Rea, Livia Visai, Angela Maria Rizzo
Summary: For the first time, this study characterizes the morphological, biochemical, and molecular changes in human bone marrow stromal cells during long-term simulated microgravity exposure. It reveals that simulated microgravity affects osteogenic differentiation and energy metabolism, and identifies dysregulated proteins that may be potential targets for future translational projects. The findings provide insights into the cell response to simulated microgravity and suggest the application of nanomaterials for mitigating the effects of microgravity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Liu He, Lotte van Beem, Berend Snel, Casper C. Hoogenraad, Martin Harterink
Summary: The neuronal microtubule cytoskeleton is crucial for establishing the polarity of axons and dendrites. In this study using Caenorhabditis elegans as a model, the roles of two microtubule minus-end related proteins, CAMSAP and NINEIN, in microtubule organization in dendrites were characterized. The results showed that CAMSAP and NINEIN function in parallel to mediate the correct orientation of microtubules in dendrites. RAB-11-positive vesicles were found to nucleate microtubules and act as a microtubule organizing center (MTOC) during dendrite outgrowth. CAMSAP and NINEIN were both important for localizing MTOC vesicles to the growing dendrite tip and organizing microtubules minus-end out.
Article
Neurosciences
Dani Flinkman, Ye Hong, Jelena Gnjatovic, Prasannakumar Deshpande, Zsuzsanna Ortutay, Sirkku Peltonen, Valtteri Kaasinen, Peter James, Eleanor Coffey
Summary: Deficits in protein synthesis are associated with Parkinson's disease (PD). We conducted a study to identify the specific proteins affected and differences in synthesis between sporadic and LRRK2-G2019S PD patients. Through proteomic analysis, we found that regulators of endo-lysosomal sorting, mRNA processing, and components of the translation machinery were consistently low in both sporadic and LRRK2-G2019S PD patients. This study provides valuable insights into the dysregulation of proteostasis in PD.
NPJ PARKINSONS DISEASE
(2023)
Article
Multidisciplinary Sciences
Amelie Freal, Nora Jamann, Jolijn Ten Bos, Jacqueline Jansen, Naomi Petersen, Thijmen Ligthart, Casper C. Hoogenraad, Maarten H. P. Kole
Summary: This study reveals the molecular mechanisms underlying the plasticity of the axon initial segment (AIS) in response to changes in network activity, showing that the activation of N-methyl-D-aspartate receptors leads to internalization of sodium channels and an increase in action potential threshold.