keyword
MENU ▼
Read by QxMD icon Read
search

Synaptotagmin

keyword
https://www.readbyqxmd.com/read/29335280/mapping-protein-interactions-of-sodium-channel-nav1-7-using-epitope-tagged-gene-targeted-mice
#1
Alexandros H Kanellopoulos, Jennifer Koenig, Honglei Huang, Martina Pyrski, Queensta Millet, Stéphane Lolignier, Toru Morohashi, Samuel J Gossage, Maude Jay, John E Linley, Georgios Baskozos, Benedikt M Kessler, James J Cox, Annette C Dolphin, Frank Zufall, John N Wood, Jing Zhao
The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. We generated an epitope-tagged NaV1.7 mouse that showed normal pain behaviours to identify channel-interacting proteins. Analysis of NaV1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 proteins associated with Nav1.7 in vivo The sodium channel β3 (Scn3b), rather than the β1 subunit, complexes with Nav1.7, and we demonstrate an interaction between collapsing-response mediator protein (Crmp2) and Nav1...
January 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29324989/synaptic-markers-of-cognitive-decline-in-neurodegenerative-diseases-a-proteomic-approach
#2
Erika Bereczki, Rui M Branca, Paul T Francis, Joana B Pereira, Jean-Ha Baek, Tibor Hortobágyi, Bengt Winblad, Clive Ballard, Janne Lehtiö, Dag Aarsland
Cognitive changes occurring throughout the pathogenesis of neurodegenerative diseases are directly linked to synaptic loss. We used in-depth proteomics to compare 32 post-mortem human brains in the prefrontal cortex of prospectively followed patients with Alzheimer's disease, Parkinson's disease with dementia, dementia with Lewy bodies and older adults without dementia. In total, we identified 10 325 proteins, 851 of which were synaptic proteins. Levels of 25 synaptic proteins were significantly altered in the various dementia groups...
January 9, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29311685/synaptotagmin-11-is-a-critical-mediator-of-parkin-linked-neurotoxicity-and-parkinson-s-disease-like-pathology
#3
Changhe Wang, Xinjiang Kang, Li Zhou, Zuying Chai, Qihui Wu, Rong Huang, Huadong Xu, Meiqin Hu, Xiaoxuan Sun, Suhua Sun, Jie Li, Ruiying Jiao, Panli Zuo, Lianghong Zheng, Zhenyu Yue, Zhuan Zhou
Loss-of-function mutations in Parkin are the most common causes of autosomal recessive Parkinson's disease (PD). Many putative substrates of parkin have been reported; their pathogenic roles, however, remain obscure due to poor characterization, particularly in vivo. Here, we show that synaptotagmin-11, encoded by a PD-risk gene SYT11, is a physiological substrate of parkin and plays critical roles in mediating parkin-linked neurotoxicity. Unilateral overexpression of full-length, but not C2B-truncated, synaptotagmin-11 in the substantia nigra pars compacta (SNpc) impairs ipsilateral striatal dopamine release, causes late-onset degeneration of dopaminergic neurons, and induces progressive contralateral motor abnormalities...
January 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29295561/exploring-the-mechanisms-of-electroacupuncture-induced-analgesia-through-rna-sequencing-of-the-periaqueductal-gray
#4
Man-Li Hu, Hong-Mei Zhu, Qiu-Lin Zhang, Jing-Jing Liu, Yi Ding, Ju-Ming Zhong, Vitaly Vodyanoy, Ming-Xing Ding
Electroacupuncture (EA) can relieve various pains. However, its mechanism in terms of the transcriptome is still not well-known. To explore the full profile of EA-induced molecular modification in the central nerve system, three twins of goats were selected for a match-paired experiment: EA stimulation (60 Hz, 30 min) and none-EA (control). Goats in the EA group showed an increased (p < 0.05) nociceptive threshold compared with the control goats. Experimental goats were sacrificed at 4 h of the experiment, and the periaqueductal grays were harvested for RNA sequencing...
December 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29289693/manganese-induced-alpha-synuclein-overexpression-impairs-synaptic-vesicle-fusion-by-disrupting-the-rab3-cycle-in-primary-cultured-neurons
#5
Tong-Yu Wang, Zhuo Ma, Can Wang, Chang Liu, Dong-Ying Yan, Yu Deng, Wei Liu, Zhao-Fa Xu, Bin Xu
Overexposure to Manganese (Mn) has been known to disrupt neurotransmitter release in the brain. However, the underlying mechanisms of Mn exposure on neurotransmitter vesicle release are still unclear. The current study investigated whether Mn-induced alpha-synuclein protein overexpression could disrupt the Rab3 cycle leading to synaptic vesicle fusion dysfunction. After the neurons were exposed to Mn (100 μM) for 0, 6, 12, 24 h, [Ca2+]i, alpha-synuclein and Rab3A-GTP protein expression increased gradually...
December 28, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29274878/immunochemical-analysis-of-the-expression-of-sv2c-in-mouse-macaque-and-human-brain
#6
Amy R Dunn, Carlie A Hoffman, Kristen A Stout, Minagi Ozawa, Rohan K Dhamsania, Gary W Miller
The synaptic vesicle glycoprotein 2C (SV2C) is an undercharacterized protein with enriched expression in phylogenetically old brain regions. Its precise role within the brain is unclear, though various lines of evidence suggest that SV2C is involved in the function of synaptic vesicles through the regulation of vesicular trafficking, calcium-induced exocytosis, or synaptotagmin function. SV2C has been linked to multiple neurological disorders, including Parkinson's disease and psychiatric conditions. SV2C is expressed in various cell types-primarily dopaminergic, GABAergic, and cholinergic cells...
December 21, 2017: Brain Research
https://www.readbyqxmd.com/read/29274147/doc2b-acts-as-a-calcium-sensor-for-vesicle-priming-requiring-synaptotagmin-1-munc13-2-and-snares
#7
Sébastien Houy, Alexander J Groffen, Iwona Ziomkiewicz, Matthijs Verhage, Paulo S Pinheiro, Jakob Balslev Sørensen
Doc2B is a cytosolic protein with binding sites for Munc13 and Tctex-1 (dynein light chain), and two C2-domains that bind to phospholipids, Ca2+ and SNAREs. Whether Doc2B functions as a calcium sensor akin to synaptotagmins, or in other calcium-independent or calcium-dependent capacities is debated. We here show by mutation and overexpression that Doc2B plays distinct roles in two sequential priming steps in mouse adrenal chromaffin cells. Mutating Ca2+-coordinating aspartates in the C2A-domain localizes Doc2B permanently at the plasma membrane, and renders an upstream priming step Ca2+-independent, whereas a separate function in downstream priming depends on SNARE-binding, Ca2+-binding to the C2B-domain of Doc2B, interaction with ubMunc13-2 and the presence of synaptotagmin-1...
December 23, 2017: ELife
https://www.readbyqxmd.com/read/29230057/synaptotagmin-1-drives-synchronous-ca2-triggered-fusion-by-c2b-domain-mediated-synaptic-vesicle-membrane-attachment
#8
Shuwen Chang, Thorsten Trimbuch, Christian Rosenmund
The synaptic vesicle (SV) protein synaptotagmin-1 (Syt1) is the Ca2+ sensor for fast synchronous release. Biochemical and structural data suggest that Syt1 interacts with phospholipids and SNARE complex, but the manner in which these interactions translate into SV fusion remains poorly understood. Using flash-and-freeze electron microscopy, which triggers action potentials with light and coordinately arrests synaptic structures with rapid freezing, we found that synchronous-release-impairing mutations in the Syt1 C2B domain (K325, 327; R398, 399) also disrupt SV-active-zone plasma-membrane attachment...
January 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29222176/ca2-releases-e-syt1-autoinhibition-to-couple-er-plasma-membrane-tethering-with-lipid-transport
#9
Xin Bian, Yasunori Saheki, Pietro De Camilli
The extended synaptotagmins (E-Syts) are endoplasmic reticulum (ER) proteins that bind the plasma membrane (PM) via C2 domains and transport lipids between them via SMP domains. E-Syt1 tethers and transports lipids in a Ca2+-dependent manner, but the role of Ca2+ in this regulation is unclear. Of the five C2 domains of E-Syt1, only C2A and C2C contain Ca2+-binding sites. Using liposome-based assays, we show that Ca2+ binding to C2C promotes E-Syt1-mediated membrane tethering by releasing an inhibition that prevents C2E from interacting with PI(4,5)P2-rich membranes, as previously suggested by studies in semi-permeabilized cells...
December 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29206031/chemoselective-installation-of-amine-bonds-on-proteins-through-aza-michael-ligation
#10
Allyson M Freedy, Maria J Matos, Omar Boutureira, Francisco Corzana, Ana Guerreiro, Padma Akkapeddi, Víctor J Somovilla, Tiago Rodrigues, Karl Nicholls, Bangwen Xie, Gonzalo Jiménez-Osés, Kevin M Brindle, André A Neves, Gonçalo J L Bernardes
Chemical modification of proteins is essential for a variety of important diagnostic and therapeutic applications. Many strategies developed to date lack chemo- and regioselectivity as well as result in non-native linkages that may suffer from instability in vivo and adversely affect the protein's structure and function. We describe here the reaction of N-nucleophiles with the amino acid dehydroalanine (Dha) in a protein context. When Dha is chemically installed in proteins, the addition of a wide-range N-nucleophiles enables the rapid formation of amine linkages (secondary and tertiary) in a chemoselective manner under mild, biocompatible conditions...
December 5, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29187811/productive-and-non-productive-pathways-for-synaptotagmin-1-to-support-ca2-triggered-fast-exocytosis
#11
Jaewook Kim, Yeon-Kyun Shin
Ca2+-triggered SNARE-mediated membrane fusion is essential for neuronal communication. The speed of this process is of particular importance because it sets a time limit to cognitive and physical activities. In this work, we expand the proteoliposome-to-supported bilayer (SBL) fusion assay by successfully incorporating synaptotagmin 1 (Syt1), a major Ca2+ sensor. We report that Syt1 and Ca2+ together can elicit more than a 50-fold increase in the number of membrane fusion events when compared with membrane fusion mediated by SNAREs only...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29166604/capture-of-dense-core-vesicles-at-synapses-by-jnk-dependent-phosphorylation-of-synaptotagmin-4
#12
Vinita Bharat, Michael Siebrecht, Katja Burk, Saheeb Ahmed, Carsten Reissner, Mahdokht Kohansal-Nodehi, Vicky Steubler, Markus Zweckstetter, Jonathan T Ting, Camin Dean
Delivery of neurotrophins and neuropeptides via long-range trafficking of dense core vesicles (DCVs) from the cell soma to nerve terminals is essential for synapse modulation and circuit function. But the mechanism by which transiting DCVs are captured at specific sites is unknown. Here, we discovered that Synaptotagmin-4 (Syt4) regulates the capture and spatial distribution of DCVs in hippocampal neurons. We found that DCVs are highly mobile and undergo long-range translocation but switch directions only at the distal ends of axons, revealing a circular trafficking pattern...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166601/triple-function-of-synaptotagmin-7-ensures-efficiency-of-high-frequency-transmission-at-central-gabaergic-synapses
#13
Chong Chen, Rachel Satterfield, Samuel M Young, Peter Jonas
Synaptotagmin 7 (Syt7) is thought to be a Ca(2+) sensor that mediates asynchronous transmitter release and facilitation at synapses. However, Syt7 is strongly expressed in fast-spiking, parvalbumin-expressing GABAergic interneurons, and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. To resolve this apparent contradiction, we examined the effects of genetic elimination of Syt7 on synaptic transmission at the GABAergic basket cell (BC)-Purkinje cell (PC) synapse in cerebellum...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29154949/a-novel-microscopy-based-assay-identifies-extended-synaptotagmin-1-esyt1-as-a-positive-regulator-of-anoctamin-1-traffic
#14
Joana R Lérias, Madalena C Pinto, Hugo M Botelho, Nikhil T Awatade, Margarida C Quaresma, Iris A L Silva, Podchanart Wanitchakool, Rainer Schreiber, Rainer Pepperkok, Karl Kunzelmann, Margarida D Amaral
An attractive possibility to treat Cystic Fibrosis (CF), a severe condition caused by dysfunctional CFTR, an epithelial anion channel, is through the activation of alternative (non-CFTR) anion channels. Anoctamin 1 (ANO1) was demonstrated to be a Ca(2+)-activated chloride channel (CaCC) and thus of high potential to replace CFTR. Despite that ANO1 is expressed in human lung CF tissue, it is present at the cell surface at very low levels. In addition, little is known about regulation of ANO1 traffic, namely which factors promote its plasma membrane (PM) localization...
November 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29122960/mir-335-overexpression-impairs-insulin-secretion-through-defective-priming-of-insulin-vesicles
#15
Vishal A Salunkhe, Jones K Ofori, Nikhil R Gandasi, Sofia A Salö, Sofia Hansson, Markus E Andersson, Anna Wendt, Sebastian Barg, Jonathan L S Esguerra, Lena Eliasson
MicroRNAs contribute to the maintenance of optimal cellular functions by fine-tuning protein expression levels. In the pancreatic β-cells, imbalances in the exocytotic machinery components lead to impaired insulin secretion and type 2 diabetes (T2D). We hypothesize that dysregulated miRNA expression exacerbates β-cell dysfunction, and have earlier shown that islets from the diabetic GK-rat model have increased expression of miRNAs, including miR-335-5p (miR-335). Here, we aim to determine the specific role of miR-335 during development of T2D, and the influence of this miRNA on glucose-stimulated insulin secretion and Ca(2+)-dependent exocytosis...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29110470/emerging-functional-differences-between-the-synaptotagmin-and-ferlin-calcium-sensor-families
#16
Colin P Johnson
The ferlin family of proteins have emerged as multi-C2 domain regulators of calcium triggered membrane fusion and fission events. While initially determined to share many of the features of the synaptotagmins family of calcium sensors, more recent studies have determined that ferlins directly interact with non-neuronal voltage gated calcium channels and nucleate the assembly of membrane trafficking protein complexes, functions that distinguish them from the more well studied synaptotagmins family. Here we highlight some of the recent findings that have advanced our understanding of ferlins and their functional differences with the synaptotagmins family...
November 7, 2017: Biochemistry
https://www.readbyqxmd.com/read/29105522/orb2-as-modulator-of-brat-and-their-role-at-the-neuromuscular-junction
#17
Elena Santana, Sergio Casas-Tintó
How synapses are built and dismantled is a central question in neurobiology. A wide range of proteins and processes from gene transcription to protein degradation are involved. Orb2 regulates mRNA translation depending on its monomeric or oligomeric state to modulate nervous system development and memory. Orb2 is expressed in Drosophila larval brain and neuromuscular junction (NMJ), Orb2 knockdown causes a reduction of synapse number and defects in neuronal morphology. Brain tumor (Brat) is an Orb2 target; it is expressed in larval brain related with cell growth and proliferation...
November 6, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/29097544/er-mitochondria-tethering-by-pdzd8-regulates-ca-2-dynamics-in-mammalian-neurons
#18
Yusuke Hirabayashi, Seok-Kyu Kwon, Hunki Paek, Wolfgang M Pernice, Maëla A Paul, Jinoh Lee, Parsa Erfani, Ashleigh Raczkowski, Donald S Petrey, Liza A Pon, Franck Polleux
Interfaces between organelles are emerging as critical platforms for many biological responses in eukaryotic cells. In yeast, the ERMES complex is an endoplasmic reticulum (ER)-mitochondria tether composed of four proteins, three of which contain a SMP (synaptotagmin-like mitochondrial-lipid binding protein) domain. No functional ortholog for any ERMES protein has been identified in metazoans. Here, we identified PDZD8 as an ER protein present at ER-mitochondria contacts. The SMP domain of PDZD8 is functionally orthologous to the SMP domain found in yeast Mmm1...
November 3, 2017: Science
https://www.readbyqxmd.com/read/29083305/single-molecule-force-spectroscopy-of-protein-membrane-interactions
#19
Lu Ma, Yiying Cai, Yanghui Li, Junyi Jiao, Zhenyong Wu, Ben O'Shaughnessy, Pietro De Camilli, Erdem Karatekin, Yongli Zhang
Many biological processes rely on protein-membrane interactions in the presence of mechanical forces, yet high resolution methods to quantify such interactions are lacking. Here, we describe a single-molecule force spectroscopy approach to quantify membrane binding of C2 domains in Synaptotagmin-1 (Syt1) and Extended Synaptotagmin-2 (E-Syt2). Syts and E-Syts bind the plasma membrane via multiple C2 domains, bridging the plasma membrane with synaptic vesicles or endoplasmic reticulum to regulate membrane fusion or lipid exchange, respectively...
October 30, 2017: ELife
https://www.readbyqxmd.com/read/29078410/crystal-structures-of-mmm1-and-mdm12-mmm1-reveal-mechanistic-insight-into-phospholipid-trafficking-at-er-mitochondria-contact-sites
#20
Hanbin Jeong, Jumi Park, Youngsoo Jun, Changwook Lee
The endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES) comprises mitochondrial distribution and morphology 12 (Mdm12), maintenance of mitochondrial morphology 1 (Mmm1), Mdm34, and Mdm10 and mediates physical membrane contact sites and nonvesicular lipid trafficking between the ER and mitochondria in yeast. Herein, we report two crystal structures of the synaptotagmin-like mitochondrial lipid-binding protein (SMP) domain of Mmm1 and the Mdm12-Mmm1 complex at 2.8 Å and 3.8 Å resolution, respectively...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
keyword
keyword
32963
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"