Article
Biology
Chao Tan, Giovanni de Nola, Claire Qiao, Cordelia Imig, Richard T. Born, Nils Brose, Pascal S. Kaeser
Summary: Active zone-anchored Munc13 and non-active zone-anchored Munc13 may independently support vesicle fusion. Removal of RIM and ELKS disrupts vesicle docking, but other ultrastructural features remain near-normal.
Review
Cell Biology
Marianna Decet, Patrik Verstreken
Summary: Autophagy is a crucial catabolic pathway for maintaining cellular homeostasis by degrading defective proteins and organelles. In neurons, the orchestrated progression of autophagy takes place in distinct subcellular compartments. Autophagy is essential for proper synaptic function and neuronal survival, particularly in the face of challenges like distance from the soma and oxidative stress.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Yoshihiro Egashira, Ayane Kumade, Akio Ojida, Fumihito Ono
Summary: This study addresses the importance of spontaneous synaptic transmission and reveals the differences in the quantity of SVs mobilized by high-frequency action potential firing and spontaneous recycling. It also highlights the activation of distinct molecular mechanisms during prolonged AP inhibition and the characteristics of the early-onset SV population.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Wenzhang Wang, Fanpeng Zhao, Yubing Lu, Sandra L. Siedlak, Hisashi Fujioka, Hao Feng, George Perry, Xiongwei Zhu
Summary: Loss of synapses is the most significant pathological feature of Alzheimer's disease (AD) that leads to cognitive deficits. This study examined synaptic deficits in AD patients and found that mitochondrial dysfunction in both pre- and post-synaptic compartments contribute to synaptic deficits in AD. These findings provide further evidence of the importance of mitochondrial dysfunction in AD pathology.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Biology
Christian Keine, Mohammed Al-Yaari, Tamara Radulovic, Connon Thomas, Paula Valino Ramos, Debbie Guerrero-Given, Mrinalini Ranjan, Holger Taschenberger, Naomi Kamasawa, Samuel M. Young
Summary: This study reveals the key regulatory role of Rac1 in synaptic transmission, mainly through modulating the dynamics of synaptic vesicle priming and potentially the release probability, affecting synaptic strength and short-term plasticity.
Article
Cell Biology
Beyenech Binotti, Momchil Ninov, Andreia P. Cepeda, Marcelo Ganzella, Ulf Matti, Dietmar Riedel, Henning Urlaub, Sivakumar Sambandan, Reinhard Jahn
Summary: The study shows that ATG9-containing vesicles are enriched in synapses and resemble synaptic vesicles in size and density. These vesicles represent a distinct population with limited overlap with synaptic vesicles and other membranes of the secretory pathway, revealing surprising heterogeneity in their membrane composition. ATG9-containing vesicles may function as lipid shuttles that scavenge membrane lipids from various intracellular membranes to support autophagosome biogenesis.
Article
Multidisciplinary Sciences
Abhijith Radhakrishnan, Xia Li, Kirill Grushin, Shyam S. Krishnakumar, Jun Liu, James E. Rothman
Summary: The controlled release of neurotransmitters stored in synaptic vesicles is essential for information processing in the brain, relying on the fusion of vesicles with presynaptic Ca2+ influx. Through cryoelectron tomography analysis, it was found that vesicles are initially tethered to the plasma membrane by protein densities under native conditions. During the process of priming for release, a highly cooperative framework is formed between the primed vesicles and the membrane, facilitating rapid neurotransmitter release following Ca2+ influx.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Chris S. Mesnard, Cody L. Barta, Asia L. Sladek, David Zenisek, Wallace B. Thoreson
Summary: The release of glutamate from rod and cone photoreceptor cells is facilitated by presynaptic ribbons composed mainly of the protein RIBEYE. The absence of ribbons in these cells leads to reduced temporal resolution, contrast sensitivity, and b-waves. The readily releasable pool of vesicles and the speed of vesicle replenishment are also reduced in cells lacking ribbons. Our findings suggest that synaptic ribbons play a crucial role in enhancing the release of vesicles and maintaining proper visual responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Carolina Montenegro-Venegas, Debarpan Guhathakurta, Eneko Pina-Fernandez, Maria Andres-Alonso, Florian Plattner, Eckart D. Gundelfinger, Anna Fejtova
Summary: This study reveals that the protein bassoon organizes the release of neurotransmitters by regulating synaptic phosphorylation and cAMP homeostasis. Synapses lacking bassoon exhibit decreased release competence of synaptic vesicles and increased resting pool of vesicles. Furthermore, the CDK5/PDE4/cAMP signaling pathway plays a crucial role in the regulation of neurotransmitter release.
Article
Neurosciences
Kosala N. Dissanayake, Filip Margetiny, Charlotte L. Whitmore, Robert C-C Chou, Cornelia Roesl, Vishwendra Patel, Joseph J. McArdle, Richard Webster, David Beeson, John E. H. Tattersall, David J. A. Wyllie, Michael Eddleston, Richard R. Ribchester
Summary: Intentional ingestion of agricultural organophosphorus insecticides is a significant public health issue in rural Asia, leading to thousands of deaths annually. Cyclohexanol alters synaptic transmission at neuromuscular junctions, reducing postsynaptic sensitivity to acetylcholine while enhancing evoked transmitter release.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Cell Biology
Julia Solana-Balaguer, Genis Campoy-Campos, Nuria Martin-Flores, Leticia Perez-Sisques, Laia Sitja-Roqueta, Melike Kucukerden, Ana Gamez-Valero, Albert Coll-Manzano, Eulalia Marti, Esther Perez-Navarro, Jordi Alberch, Jordi Soriano, Merce Masana, Cristina Malagelada
Summary: Extracellular vesicles, specifically neuron-derived EVs, play a crucial role in intercellular communication within the central nervous system. These EVs carry signaling molecules and exert a trophic effect on neurons, influencing synaptic events and promoting neuronal protection.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Neurosciences
Maya G. Feldthouse, Nicholas P. Vyleta, Stephen M. Smith
Summary: This study investigates the role of phospholipase C (PLC) in mediating the relationship between extracellular calcium concentration and spontaneous glutamate release in neurons. The findings suggest that PLC may modulate spontaneous release by modifying the size of the readily releasable pool (RRP), but the specific role of PLC-beta 1 in this process remains unclear.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Fan Fan, Yumei Wu, Manami Hara, Adam Rizk, Chen Ji, Dan Nerad, Natalia Tamarina, Xuelin Lou
Summary: This study revealed the crucial role of dynamins in endocytosis and secretion capacity of pancreatic beta cells, indicating that deficiency in dynamin-mediated endocytosis can lead to impaired insulin secretion, increasing the risk of endocrine dysfunction and diabetes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Zhe Feng, Xiandeng Wu, Mingjie Zhang
Summary: Neuronal synapses consist of three compartments: presynaptic axon terminal, synaptic cleft, and postsynaptic dendrite, each densely packed with molecular machineries involved in synaptic transmission. Recent studies suggest that the assembly of these compartments is driven by liquid-liquid phase separation, forming membraneless substructures or assemblies.
Article
Neurosciences
Jiaqi Keith Luo, Holly Melland, Jess Nithianantharajah, Sarah L. Gordon
Summary: Nlgn1 plays a crucial role in coordinating pre- and postsynaptic alignment at excitatory synapses, impacting postsynaptic transmission and plasticity. Loss of Nlgn1 does not affect vesicle release or exocytosis, but significantly impacts synaptic vesicle retrieval through compensatory endocytosis during activity. This suggests that synaptic adhesion molecules like Nlgn1 are important for regulating activity-induced endocytosis at the presynapse.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Jorge Ojeda, Francisca Bermedo-Garcia, Viviana Perez, Jessica Mella, Patricia Hanna, Daniel Herzberg, Rocio Tejero, Mario Lopez-Manzaneda, Lucia Tabares, Juan Pablo Henriquez
FRONTIERS IN CELLULAR NEUROSCIENCE
(2020)
Article
Clinical Neurology
Irene Garcia-Dominguez, Irene Suarez-Pereira, Marti Santiago, Eva M. Perez-Villegas, Lidia Bravo, Carolina Lopez-Martin, Maria Angustias Roca-Ceballos, Juan Garcia-Revilla, Ana M. Espinosa-Oliva, Jose A. Rodriguez-Gomez, Bertrand Joseph, Esther Berrocoso, Jose Angel Armengol, Jose L. Venero, Rocio Ruiz, Rocio M. de Pablos
Summary: Apoptotic caspases are crucial for synapse elimination and cell removal during development, with potential implications for neurological disorders. Depletion of caspase-3 affects the development of catecholaminergic neurons, leading to dopaminergic hypofunction. This study highlights the role of dopamine in autism spectrum disorder (ASD) and provides a valuable model for understanding ASD pathogenesis.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Mario Lopez-Manzaneda, Julio Franco-Espin, Rocio Tejero, Raquel Cano, Lucia Tabares
Summary: Spinal muscular atrophy (SMA) is a severe genetic disease in children characterized by muscle weakness and atrophy. Studies have shown that in SMA mouse models, alterations in presynaptic mitochondrial function and defects in secretion machinery play significant roles in the dysfunction of nerve terminals.
HUMAN MOLECULAR GENETICS
(2021)
Review
Geriatrics & Gerontology
Isabel M. Alonso-Bellido, Sara Bachiller, Guillermo Vazquez, Luis Cruz-Hernandez, Emilio Martinez, Ezequiel Ruiz-Mateos, Tomas Deierborg, Jose L. Venero, Luis M. Real, Rocio Ruiz
Summary: The novel coronavirus (SARS-CoV-2) has led to the global spread of COVID-19, causing respiratory symptoms such as cough and difficulty breathing, as well as various nervous system manifestations. While some patients experience acute neurological symptoms, the long-term consequences in the nervous system remain unclear.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Review
Cell Biology
Eva M. Perez-Villegas, Rocio Ruiz, Sara Bachiller, Francesc Ventura, Jose A. Armengol, Jose Luis Rosa
Summary: The HERC protein family plays important roles in neurodevelopment and neurodegenerative diseases. Mutations in HERC genes can lead to intellectual disability, epilepsy, dementia, and dysregulation of autophagy, resulting in cerebellar cell death and impaired motor control.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
I. Suarez-Pereira, I. Garcia-Dominguez, L. Bravo, M. Santiago, J. Garcia-Revilla, A. M. Espinosa-Oliva, I. M. Alonso-Bellido, C. Lopez-Martin, E. M. Perez-Villegas, J. A. Armengol, E. Berrocoso, J. L. Venero, R. M. de Pablos, R. Ruiz
Summary: New non-apoptotic roles have been discovered for apoptotic caspases, which are important in shaping the brain during early development by eliminating excessive and nonfunctional synapses and cells. Impairments in this process can contribute to neurological and mental illnesses. Additionally, low dopamine functioning appears to be associated with autism spectrum disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Israel Olivas-Martinez, Isaac Rosado-Sanchez, Juan Antonio Cordero-Varela, Salvador Sobrino, Miguel Genebat, Ines Herrero-Fernandez, Rocio Martinez de Pablos, Ana Eloisa Carvajal, Rocio Ruiz, Ana Isabel Alvarez-Rios, Maria Fontillon-Alberdi, Angel Bulnes-Ramos, Vanesa Garrido-Rodriguez, Maria del Mar Pozo-Balado, Manuel Leal, Yolanda Maria Pacheco
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Neurosciences
Mario Lopez-Manzaneda, Andrea Fuentes-Moliz, Lucia Tabares
Summary: Presynaptic mitochondria play a critical role in regulating Ca2+ signaling during neurotransmitter release. They control the size and spread of Ca2+ wave during sustained electrical activity and also contribute to the regulation of fusion mode and kinetics of vesicle release and replenishment. This study provides insights into how mitochondria modulate the timing and reliability of neurotransmission during brief action potential trains in motor nerve terminals.
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2022)
Article
Biology
Francisca Bermedo-Garcia, Diego Zelada, Esperanza Martinez, Lucia Tabares, Juan Pablo Henriquez
Summary: Research shows that reversible nerve damage leaves a long-lasting impact on the NMJ, resulting in rearrangement of its cellular components. These features actually represent an efficient adaptive response for functional recovery.
Review
Cell Biology
Juan Garcia-Revilla, Antonio Boza-Serrano, Ana M. Espinosa-Oliva, Manuel Sarmiento Soto, Tomas Deierborg, Rocio Ruiz, Rocio M. de Pablos, Miguel Angel Burguillos, Jose L. Venero
Summary: The high-throughput single-cell transcriptomic analysis technique has revealed common characteristics of galectin-3 upregulation in disease-associated microglia. The ability of galectin-3 to interact with key pattern recognition receptors has been demonstrated, and increasing evidence supports its involvement in major neurodegenerative diseases.
CELL DEATH & DISEASE
(2022)
Editorial Material
Neurosciences
Lucia Tabares, Silvio O. Rizzoli
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Julio Franco-Espin, Alao Gatius, Jose Angel Armengol, Saravanan Arumugam, Mehri Moradi, Michael Sendtner, Jordi Caldero, Lucia Tabares
Summary: SMN protein appears as granules distributed along motor axons at nerve terminals, which co-localize with microtubule-associated protein 1B and neurofilaments. In presynaptic motor terminals, β-actin mRNA, ribosomes, and polysomes, which are key elements of the protein synthesis machinery involved in local translation, are also present. In SMA mice, SMN granules accumulate in areas of neurofilament aggregation, potentially impairing the bi-directional traffic of proteins and organelles between the axon and the presynaptic terminal.
Article
Biochemistry & Molecular Biology
Rocio Tejero, Mohammad Alsakkal, Luisa Hennlein, Ana M. Lopez-Cabello, Sibylle Jablonka, Lucia Tabares
Summary: In spinal muscular atrophy (SMA), mutations in the SMN1 gene reduce full-length SMN protein which causes motor neuron degeneration. Nifedipine was found to improve the function of spinal cord motor neurons and motor nerve terminals in cultured cells of SMA mice. It increased neurotransmission and prevented developmental defects in SMA neurons, indicating its potential therapeutic effects for SMA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Vassilis Stratoulias, Rocio Ruiz, Shigeaki Kanatani, Ahmed M. Osman, Lily Keane, Jose A. Armengol, Antonio Rodriguez-Moreno, Adriana-Natalia Murgoci, Irene Garcia-Dominguez, Isabel Alonso-Bellido, Fernando Gonzalez Ibanez, Katherine Picard, Guillermo Vazquez-Cabrera, Mercedes Posada-Perez, Nathalie Vernoux, Dario Tejera, Kathleen Grabert, Mathilde Cheray, Patricia Gonzalez-Rodriguez, Eva M. Perez-Villegas, Irene Martinez-Gallego, Alejandro Lastra-Romero, David Brodin, Javier Avila-Carino, Yang Cao, Mikko Airavaara, Per Uhlen, Michael T. Heneka, Marie-Eve Tremblay, Klas Blomgren, Jose L. Venero, Bertrand Joseph
Summary: The molecular diversity of microglia in the CNS has been described. The study shows that microglia expressing the enzyme ARG1 are enriched in phagocytic inclusions and play a role in hippocampal innervation and spine maturation in mice. ARG1-expressing microglia also influence cognition in a sex-dependent manner.
NATURE NEUROSCIENCE
(2023)
Article
Cell Biology
Dominic Tscherrig, Rajesh Bhardwaj, Daniel Biner, Jan Dernic, Daniela Ross-Kaschitza, Christine Peinelt, Matthias A. Hediger, Martin Lochner
Summary: Changes in Ca2+ levels regulate many physiological functions, and the endoplasmic reticulum is the major Ca2+ store in cells. Store-operated calcium entry (SOCE) is a refilling process that involves protein-protein interactions between Ca2+ sensing STIM in the ER and Orai proteins in the plasma membrane, forming selective Ca2+ channels. Abnormal SOCE is associated with diseases and cancers, making STIM and Orai important therapeutic targets. Novel GSK-7975A-based molecular probes have been developed for studying SOCE in different cells and settings.
Article
Cell Biology
Nicola Fameli, Cornelis van Breemen, Klaus Groschner
Summary: The study provides evidence for the importance of junctional membrane architecture in cellular function. Through modeling and prediction, it is shown that nano-scale membrane spacing plays a crucial role in junctional ER Ca2+ refilling and signaling efficiency. Additionally, interactions between Ca2+ and the phospholipid membrane surface are suggested to support interfacial Ca2+ transport and receptor targeting. This research introduces a new concept in pathophysiology.
Article
Cell Biology
Satomi Ohtsuka, Yumi Miyai, Hiroyuki Mima, Masaki Magari, Yoichi Chiba, Futoshi Suizu, Hiroyuki Sakagami, Masaki Ueno, Hiroshi Tokumitsu
Summary: This study characterized the splice variants of mouse CaMKKI3/2 and found that CaMKKI3-3 and I3-3x were functionally active and likely to be bona fide CaMKIV kinases involved in the regulation of spermiogenesis.
