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https://www.readbyqxmd.com/read/29760652/cadherins-interact-with-synaptic-organizers-to-promote-synaptic-differentiation
#1
Masahito Yamagata, Xin Duan, Joshua R Sanes
Classical cadherins, a set of ~20 related recognition and signaling molecules, have been implicated in many aspects of neural development, including the formation and remodeling of synapses. Mechanisms underlying some of these steps have been studied by expressing N-cadherin ( cdh2 ), a Type 1 cadherin, in heterologous cells, but analysis is complicated because widely used lines express cdh2 endogenously. We used CRISPR-mediated gene editing to generate a Human embryonic kidney (HEK)293 variant lacking Cdh2, then compared the behavior of rodent cortical and hippocampal neurons co-cultured with parental, cdh2 mutant and cdh2 -rescued 293 lines...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29748690/untargeted-lipidomic-analysis-of-primary-human-epidermal-melanocytes-acutely-and-chronically-exposed-to-uv-radiation
#2
Núria Dalmau, Nathalie Andrieu-Abadie, Romà Tauler, Carmen Bedia
Ultraviolet (UV) radiation present in sunlight has been related to harmful effects on skin such as premature aging and skin cancer. In order to study the effects of UV radiation on skin, many investigations have been carried out at transcriptomic and proteomic levels. However, studies on the effects of UV radiation on lipid composition are scarce. In this work, primary cultures of melanocytes were exposed to UV radiation in a similar UVA/UVB ratio to that found in solar light. The UV exposure was carried out twice a week and different endpoints were investigated at 0...
May 11, 2018: Molecular omics
https://www.readbyqxmd.com/read/29567418/plasticizer-di-2-ethylhexyl-phthalate-dehp-enhances-cockroach-allergen-extract-driven-airway-inflammation-by-enhancing-pulmonary-th2-as-well-as-th17-immune-responses-in-mice
#3
Ali S Alfardan, Ahmed Nadeem, Sheikh F Ahmad, Naif O Al-Harbi, Mohammad M Al-Harbi, Shakir D AlSharari
In recent decades, there has been a gradual increase in the prevalence of asthma. Various factors including environmental pollutants have contributed to this phenomenon. Plasticizer, di(2-ethylhexyl)phthalate (DEHP) is one of the commonest environmental pollutants due to its association with plastic products. DEHP gets released from plastic products easily leading to respiratory exposure in humans. As a consequence, DEHP is associated with allergic asthma in humans and animals. DEHP is reported to act as an adjuvant in ovalbumin-induced mouse models of asthma at high doses...
March 19, 2018: Environmental Research
https://www.readbyqxmd.com/read/29467625/effect-of-vitamin-d-in-hn9-10e-embryonic-hippocampal-cells-and-in-hippocampus-from-mptp-induced-parkinson-s-disease-mouse-model
#4
Samuela Cataldi, Cataldo Arcuri, Stéphane Hunot, Carmen Mecca, Michela Codini, Maria E Laurenti, Ivana Ferri, Elisabetta Loreti, Mercedes Garcia-Gil, Giovanna Traina, Carmela Conte, Francesco S Ambesi-Impiombato, Tommaso Beccari, Francesco Curcio, Elisabetta Albi
It has long been proven that neurogenesis continues in the adult brains of mammals in the dentatus gyrus of the hippocampus due to the presence of neural stem cells. Although a large number of studies have been carried out to highlight the localization of vitamin D receptor in hippocampus, the expression of vitamin D receptor in neurogenic dentatus gyrus of hippocampus in Parkinson's disease (PD) and the molecular mechanisms triggered by vitamin D underlying the production of differentiated neurons from embryonic cells remain unknown...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29448069/micro-environmental-signals-directing-human-epidermal-langerhans-cell-differentiation
#5
REVIEW
Herbert Strobl, Corinna Krump, Izabela Borek
Human Langerhans cells (LC) can be generated ex vivo from hematopoietic precursor cells in response to cytokines and cell-membrane associated ligands. These in vitro differentiation models provided mechanistic insights into the molecular and cellular pathways underlying the development of this unique, epithelia-associated dendritic cell subset. Notably, the human epidermal microenvironment is fully sufficient to induce LC differentiation from hematopoietic progenitors. Hence, dissecting the molecular characteristics of the human epithelial/epidermal LC niche, and testing defined ligands for their capacity to induce LC differentiation, led to a refined molecular model of LC lineage commitment...
February 23, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29406991/a-new-etiologic-model-for-alzheimers-disease
#6
Kathryn A Schiel
This etiologic model proposes that Alzheimers Disease (AD) arises when an unusually rapid increase in ventricle volume triggers axon stretch that culminates in the physical separation of trans-synaptic proteins. As a result, these proteins, such as neurexin, neuroligin, N-Cadherin and Amyloid Precursor Protein (APP), experience a change in the configuration of their cytoplasmic tail, so that instead of transmitting signals to create and maintain synaptic structure they activate enzymes, and generate molecules, that stimulate neurite growth; for example, the transformation of the N-Cadherin tail dissolves its complex with presenilin and β-catenin triggering activation of glycogen synthase kinase 3 beta (GSK3β) and cytoskeletal disruption...
February 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29403496/recent-advances-in-targeting-cd8-t-cell-immunity-for-more-effective-cancer-immunotherapy
#7
REVIEW
Aurélie Durgeau, Yasemin Virk, Stéphanie Corgnac, Fathia Mami-Chouaib
Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including cytotoxic T-lymphocyte associated antigen (CTLA)-4 and programmed cell death (PD)-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma. PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI). Cytotoxic T lymphocytes (CTL) eliminate malignant cells through recognition by the T-cell receptor (TCR) of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I/beta-2-microglobulin complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29330091/cdc42ep4-a-perisynaptic-scaffold-protein-in-bergmann-glia-is-required-for-glutamatergic-tripartite-synapse-configuration
#8
Natsumi Ageta-Ishihara, Kohtarou Konno, Maya Yamazaki, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Makoto Kinoshita
Configuration of tripartite synapses, comprising the pre-, post-, and peri-synaptic components (axon terminal or bouton, dendritic spine, and astroglial terminal process), is a critical determinant of neurotransmitter kinetics and hence synaptic transmission. However, little is known about molecular basis for the regulation of tripartite synapse morphology. Previous studies showed that CDC42EP4, an effector protein of a cell morphogenesis regulator CDC42, is expressed exclusively in Bergmann glia in the cerebellar cortex, that it forms tight complex with the septin heterooligomer, and that it interacts indirectly with the glutamate transporter GLAST and MYH10/nonmuscle myosin ΙΙB...
January 9, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29151265/cnn3-regulates-neural-tube-morphogenesis-and-neuronal-stem-cell-properties
#9
Dirk Junghans, Sebastian Herzog
Calponin 3 (Cnn3) is a member of the Cnn family of actin-binding molecules that is highly expressed in the mammalian brain and has been shown to control dendritic spine morphology, density, and plasticity by regulating actin cytoskeletal reorganization and dynamics. However, little is known about the role of Cnn3 during embryonic development. In this study, we analyzed mutant animals deficient in Cnn3 to gain a better understanding of its role in brain morphogenesis. Embryos lacking Cnn3 exhibited massive malformation of the developing brain including exoencephaly, closure defects at the rostral neural tube, and strong enlargement of brain tissue...
January 2018: FEBS Journal
https://www.readbyqxmd.com/read/29133434/pkd1-promotes-functional-synapse-formation-coordinated-with-n-cadherin-in-hippocampus
#10
Cheng Cen, Li-Da Luo, Wen-Qi Li, Gang Li, Na-Xi Tian, Ge Zheng, Dong-Min Yin, Yimin Zou, Yun Wang
Functional synapse formation is critical for the wiring of neural circuits in the developing brain. The cell adhesion molecule N-cadherin plays important roles in target recognition and synaptogenesis. However, the molecular mechanisms that regulate the localization of N-cadherin and the subsequent effects remain poorly understood. Here, we show that protein kinase D1 (PKD1) directly binds to N-cadherin at amino acid residues 836-871 and phosphorylates it at Ser 869, 871, and 872, thereby increasing the surface localization of N-cadherin and promoting functional synapse formation in primary cultured hippocampal neurons obtained from embryonic day 18 rat embryos of either sex...
January 3, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29030434/cadherin-10-maintains-excitatory-inhibitory-ratio-through-interactions-with-synaptic-proteins
#11
Katharine R Smith, Kelly A Jones, Katherine J Kopeikina, Alain C Burette, Bryan A Copits, Sehyoun Yoon, Marc P Forrest, Jessica M Fawcett-Patel, Jonathan G Hanley, Richard J Weinberg, Geoffrey T Swanson, Peter Penzes
Appropriate excitatory/inhibitory (E/I) balance is essential for normal cortical function and is altered in some psychiatric disorders, including autism spectrum disorders (ASDs). Cell-autonomous molecular mechanisms that control the balance of excitatory and inhibitory synapse function remain poorly understood; no proteins that regulate excitatory and inhibitory synapse strength in a coordinated reciprocal manner have been identified. Using super-resolution imaging, electrophysiology, and molecular manipulations, we show that cadherin-10, encoded by CDH10 within the ASD risk locus 5p14...
November 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28978039/antitumor-immunity-induced-by-ve-cadherin-modified-dc-vaccine
#12
Jing Zhou, Yufeng Xi, Xiyan Mu, Rongce Zhao, Hongdou Chen, Li Zhang, Yang Wu, Qiu Li
Dendritic cells (DCs) are the most potent antigen-presenting cells. A strong interest has been developed in DC vaccines for cancer immunotherapy. Besides, angiogenesis is essential for tumor growth. VE-cadherin has a crucial function in various aspects of vascular biological functions. Here, we produced the full VE-cadherin gene modified DC vaccine (DC-VEC). Its antitumor immunity and chief mechanism driving antitumor effect was evaluated. Analyses were performed including test of antitumor antibody, CTL-mediated cytotoxicity experiment, vascular density, evaluation of the variation of cells and cytokines in immunoregulation...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28960088/adam10-as-a-therapeutic-target-for-brain-diseases-from-developmental-disorders-to-alzheimer-s-disease
#13
REVIEW
Elena Marcello, Barbara Borroni, Silvia Pelucchi, Fabrizio Gardoni, Monica Di Luca
In the central nervous system a disintegrin and metalloproteinase 10 (ADAM10) controls several functions such as neurodevelopment, synaptic plasticity and dendritic spine morphology thanks to its activity towards a high number of substrates, including the synaptic cell adhesion molecules as the Amyloid Precursor Protein, N-cadherin, Notch and Ephrins. In particular, ADAM10 plays a key role in the modulation of the molecular mechanisms responsible for dendritic spine formation, maturation and stabilization and in the regulation of the molecular organization of the glutamatergic synapse...
November 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28756270/neuronal-territory-formation-by-the-atypical-cadherins-and-clustered-protocadherins
#14
REVIEW
Julie L Lefebvre
Spatial patterns of neuronal connectivity are critical for neural circuit function and information processing. For many neuron types, the development of stereotyped dendritic and axonal territories involves reiterative contacts between neurites and successive re-calibration of branch outgrowth and directionality. Here I review emerging roles for members of the atypical cadherins (Fmi/Celsrs) and the clustered Protocadherins (Pcdhs) in neurite patterning. These cell-surface molecules have shared functions: they engage in homophilic recognition and mediate dynamic and contact-dependent interactions to establish reproducible and space-filling arborization patterns...
July 27, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28729535/pld1-promotes-dendritic-spine-development-by-inhibiting-adam10-mediated-n-cadherin-cleavage
#15
Li-Da Luo, Gang Li, Yun Wang
Synapses are the basic units of information transmission, processing and integration in the nervous system. Dysfunction of the synaptic development has been recognized as one of the main reasons for mental dementia and psychiatric diseases such as Alzheimer's disease and autism. However, the underlying mechanisms of the synapse formation are far from clear. Here we report that phospholipase D1 (PLD1) promotes the development of dendritic spines in hippocampal neurons. We found that overexpressing PLD1 increases both the density and the area of dendritic spines...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28666264/antitumor-immunity-induced-by-ve-cadherin-modified-dc-vaccine
#16
Jing Zhou, Yufeng Xi, Xiyan Mu, Rongce Zhao, Hongdou Chen, Li Zhang, Yang Wu, Qiu Li
Dendritic cells (DCs) are the most potent antigen-presenting cells. A strong interest has been developed in DC vaccines for cancer immunotherapy. Besides, angiogenesis is essential for tumor growth. VE-cadherin has a crucial function in various aspects of vascular biological functions. Here, we produced the full VE-cadherin gene modified DC vaccine (DC-VEC). Its antitumor immunity and chief mechanism driving antitumor effect was evaluated. Analyses were performed including test of antitumor antibody, CTL-mediated cytotoxicity experiment, vascular density, evaluation of the variation of cells and cytokines in immunoregulation...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28641114/a-critical-role-of-presynaptic-cadherin-catenin-p140cap-complexes-in-stabilizing-spines-and-functional-synapses-in-the-neocortex
#17
Min-Yin Li, Wan-Ying Miao, Qiu-Zi Wu, Shun-Ji He, Guoquan Yan, Yanrui Yang, Jia-Jia Liu, M Mark Taketo, Xiang Yu
The formation of functional synapses requires coordinated assembly of presynaptic transmitter release machinery and postsynaptic trafficking of functional receptors and scaffolds. Here, we demonstrate a critical role of presynaptic cadherin/catenin cell adhesion complexes in stabilizing functional synapses and spines in the developing neocortex. Importantly, presynaptic expression of stabilized β-catenin in either layer (L) 4 excitatory neurons or L2/3 pyramidal neurons significantly upregulated excitatory synaptic transmission and dendritic spine density in L2/3 pyramidal neurons, while its sparse postsynaptic expression in L2/3 neurons had no such effects...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28636748/e-cadherin-mediates-ultraviolet-radiation-and-calcium-induced-melanin-transfer-in-human-skin-cells
#18
Suman K Singh, Richard Baker, Stephen K Sikkink, Carine Nizard, Sylvianne Schnebert, Robin Kurfurst, Desmond J Tobin
Skin pigmentation is directed by epidermal melanin units, characterized by long-lived and dendritic epidermal melanocytes (MC) that interact with viable keratinocytes (KC) to contribute melanin to the epidermis. Previously, we reported that MC:KC contact is required for melanosome transfer that can be enhanced by filopodi, and by UVR/UVA irradiation, which can upregulate melanosome transfer via Myosin X-mediated control of MC filopodia. Both MC and KC express Ca2+ -dependent E-cadherins. These homophilic adhesion contacts induce transient increases in intra-KC Ca2+ , while ultraviolet radiation (UVR) raises intra-MC Ca2+ via calcium-selective ORAI1 ion channels; both are associated with regulating melanogenesis...
November 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28631008/regulation-of-neural-circuit-formation-by-protocadherins
#19
REVIEW
Stacey L Peek, Kar Men Mah, Joshua A Weiner
The protocadherins (Pcdhs), which make up the most diverse group within the cadherin superfamily, were first discovered in the early 1990s. Data implicating the Pcdhs, including ~60 proteins encoded by the tandem Pcdha, Pcdhb, and Pcdhg gene clusters and another ~10 non-clustered Pcdhs, in the regulation of neural development have continually accumulated, with a significant expansion of the field over the past decade. Here, we review the many roles played by clustered and non-clustered Pcdhs in multiple steps important for the formation and function of neural circuits, including dendrite arborization, axon outgrowth and targeting, synaptogenesis, and synapse elimination...
November 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28498492/multiple-roles-of-afadin-in-the-ultrastructural-morphogenesis-of-mouse-hippocampal-mossy-fiber-synapses
#20
Kousyoku Sai, Shujie Wang, Aika Kaito, Takeshi Fujiwara, Tomohiko Maruo, Yu Itoh, Muneaki Miyata, Shotaro Sakakibara, Naoyuki Miyazaki, Kazuyoshi Murata, Yuuki Yamaguchi, Tomohiro Haruta, Hideo Nishioka, Yuki Motojima, Miyuki Komura, Kazushi Kimura, Kenji Mandai, Yoshimi Takai, Akira Mizoguchi
A hippocampal mossy fiber synapse, which is implicated in learning and memory, has a complex structure in which mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions (PAJs) and wrap around a multiply-branched spine, forming synaptic junctions. Here, we electron microscopically analyzed the ultrastructure of this synapse in afadin-deficient mice. Transmission electron microscopy analysis revealed that typical PAJs with prominent symmetrical plasma membrane darkening undercoated with the thick filamentous cytoskeleton were observed in the control synapse, whereas in the afadin-deficient synapse, atypical PAJs with the symmetrical plasma membrane darkening, which was much less in thickness and darkness than those of the control typical PAJs, were observed...
May 12, 2017: Journal of Comparative Neurology
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