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https://www.readbyqxmd.com/read/29151265/cnn3-regulates-neural-tube-morphogenesis-and-neuronal-stem-cell-properties
#1
Dirk Junghans, Sebastian Herzog
Calponin 3 (Cnn3) is a member of the calponin 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...
November 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29133434/pkd1-promotes-functional-synapse-formation-coordinated-with-n-cadherin-in-hippocampus
#2
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, 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...
November 13, 2017: 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
#3
Katharine R Smith, Kelly A Jones, Katherine J Kopeikina, Alain C Burette, Bryan A Copits, Sehyoun Yoon, Marc 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...
October 13, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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 Ca(2+) -dependent E-cadherins. These homophilic adhesion contacts induce transient increases in intra-KC Ca(2+) , while ultraviolet radiation (UVR) raises intra-MC Ca(2+) 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
#11
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
#12
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
https://www.readbyqxmd.com/read/28435999/neonatal-propofol-anesthesia-changes-expression-of-synaptic-plasticity-proteins-and-increases-stereotypic-and-anxyolitic-behavior-in-adult-rats
#13
Desanka Milanovic, Vesna Pesic, Natasa Loncarevic-Vasiljkovic, Vladimir Avramovic, Vesna Tesic, Vesna Jevtovic-Todorovic, Selma Kanazir, Sabera Ruzdijic
Propofol is a general anesthetic commonly used in pediatric clinical practices. Experimental findings demonstrate that anesthetics induce widespread apoptosis and cognitive decline in a developing brain. Although anesthesia-mediated neurotoxicity is the most prominent during intense period of synaptogenesis, the effects of an early anesthesia exposure on the synapses are not well understood. The aim of this study was to examine the effects of neonatal propofol anesthesia on the expression of key proteins that participate in synaptogenesis and synaptic plasticity and to evaluate long-term neurobehavioral abnormalities in the mature adult brain...
August 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/27993509/reggie-1-and-reggie-2-flotillins-participate-in-rab11a-dependent-cargo-trafficking-spine-synapse-formation-and-ltp-related-ampa-receptor-glua1-surface-exposure-in-mouse-hippocampal-neurons
#14
Vsevolod Bodrikov, Aline Pauschert, Gaga Kochlamazashvili, Claudia A O Stuermer
Reggie-1 and -2 (flotillins) reside at recycling vesicles and promote jointly with Rab11a the targeted delivery of cargo. Recycling is essential for synapse formation suggesting that reggies and Rab11a may regulate the development of spine synapses. Recycling vesicles provide cargo for dendritic growth and recycle surface glutamate receptors (AMPAR, GluA) for long-term potentiation (LTP) induced surface exposure. Here, we show reduced number of spine synapses and impairment of an in vitro correlate of LTP in hippocampal neurons from reggie-1 k...
March 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27909399/a-subset-of-autism-associated-genes-regulate-the-structural-stability-of-neurons
#15
REVIEW
Yu-Chih Lin, Jeannine A Frei, Michaela B C Kilander, Wenjuan Shen, Gene J Blatt
Autism spectrum disorder (ASD) comprises a range of neurological conditions that affect individuals' ability to communicate and interact with others. People with ASD often exhibit marked qualitative difficulties in social interaction, communication, and behavior. Alterations in neurite arborization and dendritic spine morphology, including size, shape, and number, are hallmarks of almost all neurological conditions, including ASD. As experimental evidence emerges in recent years, it becomes clear that although there is broad heterogeneity of identified autism risk genes, many of them converge into similar cellular pathways, including those regulating neurite outgrowth, synapse formation and spine stability, and synaptic plasticity...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27897208/beta-1-integrin-ligation-and-tlr-ligation-enhance-gm-csf-induced-aldh1a2-expression-in-dendritic-cells-but-differentially-regulate-their-anti-inflammatory-properties
#16
Aya Yokota-Nakatsuma, Yoshiharu Ohoka, Hajime Takeuchi, Si-Young Song, Makoto Iwata
Retinoic acid (RA)-producing CD103(+) mature dendritic cells (DCs) in mesenteric lymph nodes (MLNs) play crucial roles in gut immunity. GM-CSF and RA contribute to the expression of the RA-producing enzyme ALDH1A2. However, additional signals appeared to be required for inducing ALDH1A2(high) mature DCs from immature DCs. We found here that TLR ligands (Ls) and immobilized E-cadherin could provide such signals in FLT3-L-generated bone marrow (BM)-derived DCs after treatment with GM-CSF and the RA receptor agonist Am80...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880914/neuronal-ctcf-is-necessary-for-basal-and-experience-dependent-gene-regulation-memory-formation-and-genomic-structure-of-bdnf-and-arc
#17
Dev Sharan Sams, Stefano Nardone, Dmitriy Getselter, Dana Raz, Moran Tal, Prudhvi Raj Rayi, Hanoch Kaphzan, Ofir Hakim, Evan Elliott
CCCTC-binding factor (CTCF) is an organizer of higher-order chromatin structure and regulates gene expression. Genetic studies have implicated mutations in CTCF in intellectual disabilities. However, the role of CTCF-mediated chromatin structure in learning and memory is unclear. We show that depletion of CTCF in postmitotic neurons, or depletion in the hippocampus of adult mice through viral-mediated knockout, induces deficits in learning and memory. These deficits in learning and memory at the beginning of adulthood are correlated with impaired long-term potentiation and reduced spine density, with no changes in basal synaptic transmission and dendritic morphogenesis and arborization...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27822498/the-x-linked-autism-protein-kiaa2022-kidlia-regulates-neurite-outgrowth-via-n-cadherin-and-%C3%AE-catenin-signaling
#18
James Gilbert, Heng-Ye Man
Our previous work showed that loss of the KIAA2022 gene protein results in intellectual disability with language impairment and autistic behavior (KIDLIA, also referred to as XPN). However, the cellular and molecular alterations resulting from a loss of function of KIDLIA and its role in autism with severe intellectual disability remain unknown. Here, we show that KIDLIA plays a key role in neuron migration and morphogenesis. We found that KIDLIA is distributed exclusively in the nucleus. In the developing rat brain, it is expressed only in the cortical plate and subplate region but not in the intermediate or ventricular zone...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27788242/disparate-regulatory-mechanisms-control-fat3-and-p75ntr-protein-transport-through-a-conserved-kif5-interaction-domain
#19
Haixia Cheng, Jessica Burroughs-Garcia, Jacqueline E Birkness, Jonathan C Trinidad, Michael R Deans
Directed transport delivers proteins to specific cellular locations and is one mechanism by which cells establish and maintain polarized cellular architectures. The atypical cadherin Fat3 directs the polarized extension of dendrites in retinal amacrine cells by influencing the distribution of cytoskeletal regulators during retinal development, however the mechanisms regulating the distribution of Fat3 remain unclear. We report a novel Kinesin/Kif5 Interaction domain (Kif5-ID) in Fat3 that facilitates Kif5B binding, and determines the distribution of Fat3 cytosolic domain constructs in neurons and MDCK cells...
2016: PloS One
https://www.readbyqxmd.com/read/27784870/induction-of-langerin-langerhans-cell-like-cells-expressing-reduced-tlr3-from-cd34-cord-blood-cells-stimulated-with-gm-csf-tgf-%C3%AE-1-and-tnf-%C3%AE
#20
Hideko Azuma, Eri Watanabe, Yohei Otsuka, Yasuyuki Negishi, Sadayuki Ohkura, Eiji Shinya, Hidemi Takahashi
Langerhans cells (LCs), a subset of dendritic cells (DCs), reside in body surface presenting antigens from various pathogens and activate immune system after migrating to vicinal lymph nodes. We recently demonstrated that the E-cadherin interaction allowed peripheral blood (PB) CD14(+) cells to differentiate into LC-like cells that closely resemble primary LCs. Here, with a combination of GM-CSF, TGF-β, and TNF-α, we induced LC-like cells from umbilical cord blood (UCB)derived CD34(+) cells and compared them with those induced from PB CD14(+) cells...
2016: Biomedical Research
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