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https://www.readbyqxmd.com/read/29322779/mining-the-secretome-of-c2c12-muscle-cells-data-dependent-experimental-approach-to-analyze-protein-secretion-using-label-free-quantification-and-peptide-based-analysis
#1
Leonie Grube, Rafael Dellen, Fabian Kruse, Holger Schwender, Kai Stuehler, Gereon Poschmann
Secretome analysis faces several challenges, including detection of low abundant proteins and the discrimination of bona fide secreted proteins from false-positive identifications stemming from cell leakage or serum. Here, we developed a two-step secretomics approach and applied it to the analysis of secreted proteins of C2C12 skeletal muscle cells since the skeletal muscle has been identified as an important endocrine organ secreting myokines as signaling molecules. First, we compared culture supernatants with corresponding cell lysates by mass spectrometry-based proteomics and label-free quantification...
January 11, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29320740/plexina2-forward-signaling-through-rap1-gtpases-regulates-dentate-gyrus-development-and-schizophrenia-like-behaviors
#2
Xiao-Feng Zhao, Rafi Kohen, Rachel Parent, Yuntao Duan, Grace L Fisher, Matthew J Korn, Lingchao Ji, Guoqiang Wan, Jing Jin, Andreas W Püschel, David F Dolan, Jack M Parent, Gabriel Corfas, Geoffrey G Murphy, Roman J Giger
Dentate gyrus (DG) development requires specification of granule cell (GC) progenitors in the hippocampal neuroepithelium, as well as their proliferation and migration into the primordial DG. We identify the Plexin family members Plxna2 and Plxna4 as important regulators of DG development. Distribution of immature GCs is regulated by Sema5A signaling through PlxnA2 and requires a functional PlxnA2 GTPase-activating protein (GAP) domain and Rap1 small GTPases. In adult Plxna2-/- but not Plxna2-GAP-deficient mice, the dentate GC layer is severely malformed, neurogenesis is compromised, and mossy fibers form aberrant synaptic boutons within CA3...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29214018/transcriptional-changes-in-mesenteric-and-subcutaneous-adipose-tissue-from-holstein-cows-in-response-to-plane-of-dietary-energy
#3
S J Moisá, P Ji, J K Drackley, S L Rodriguez-Zas, J J Loor
Background: Dairy cows can readily overconsume dietary energy during most of the prepartum period, often leading to higher prepartal concentrations of insulin and glucose and excessive body fat deposition. The end result of these physiologic changes is greater adipose tissue lipolysis post-partum coupled with excessive hepatic lipid accumulation and compromised health. Although transcriptional regulation of the adipose response to energy availability is well established in non-ruminants, such regulation in cow adipose tissue depots remains poorly characterized...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29203829/il-4-driven-transcription-factor-foxq1-is-expressed-by-monocytes-in-atopic-dermatitis-and-stimulates-monocyte-migration
#4
Ilja Ovsiy, Vladimir Riabov, Ioannis Manousaridis, Julia Michel, Kondaiah Moganti, Shuiping Yin, Tengfei Liu, Carsten Sticht, Elisabeth Kremmer, Martin C Harmsen, Sergij Goerdt, Alexei Gratchev, Julia Kzhyshkowska
Monocytes are actively recruited at sites of chronic inflammation. However, molecular factors involved in this process are not fully elucidated. Here, we show that cytokine IL-4 which is implicated in the development of chronic inflammatory disease atopic dermatitis (AD) induces expression of transcription factor FoxQ1 in human monocytes and macrophages. FoxQ1 mRNA levels were elevated in monocytes of AD patients compared to healthy donors. Overexpression of FoxQ1 in RAW 264.7 monocytic cells facilitated their migration towards MCP-1 and was associated with decreased expression of migration-regulating genes (claudin 11 and plexin C1)...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29163508/interferon-%C3%AE-enhanced-cd100-plexin-b1-b2-interactions-promote-natural-killer-cell-functions-in-patients-with-chronic-hepatitis-c-virus-infection
#5
Yu He, Yonghong Guo, Chao Fan, Yingfeng Lei, Yun Zhou, Mingjie Zhang, Chuantao Ye, Guangxi Ji, Li Ma, Jianqi Lian, Jonathan P Moorman, Zhi Q Yao, Jiuping Wang, Chunqiu Hao, Ying Zhang, Zhansheng Jia
Background: CD100, also known as Sema4D, is an immune semaphorin constitutively expressed on natural killer (NK) cells and T cells. As an immune activation molecule, CD100 has important immunoregulatory effects on NK functions by enhancing the interactions between NK cells and target cells. The aim of this study was to investigate whether hepatitis C virus (HCV) infection affects CD100 expression, and whether interferon-α treatment enhances NK killing activity to facilitate HCV clearance via CD100...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29133239/emerging-role-of-plexins-signaling-in-glioma-progression-and-therapy
#6
Efthalia Angelopoulou, Christina Piperi
Gliomas are highly invasive brain tumors with increased resistance to chemotherapy and high recurrence rate. Neoplastic cells commonly infiltrate into the surrounding tissue even at low grade tumors. Cell migration is often ceased at white and grey matter junctions indicating the involvement of tropic and axon guidance molecules in glioma growth and invasion. Emerging evidence implicates plexin-semaphorin signaling in the pathobiology of gliomas. Plexins are transmembrane receptors divided into four subfamilies (Plexins-A to -D) with differential specificity and functionality...
November 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29113996/characterization-of-the-molecular-mechanisms-underlying-glucose-stimulated-insulin-secretion-from-isolated-pancreatic-%C3%AE-cells-using-ptmomics
#7
Taewook Kang, Pia Jensen, Honggang Huang, Gitte Lund Christensen, Nils Billestrup, Martin R Larsen
Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. However, the molecular mechanisms underlying the insulin secretion are unclear. Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins...
November 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29107805/neuronal-expression-patterns-of-the-plexina-family-during-zebrafish-development
#8
Sarah E Emerson, Sarah E Light, Alicia M Ebert
Plexins (Plxns) and Semaphorins (Semas) are key signaling molecules that regulate many aspects of development. Plxns are a family of transmembrane protein receptors that are activated upon extracellular binding by Semas. Activated Plxns trigger intracellular signaling cascades, which regulate a range of developmental processes, including axon guidance, neuronal positioning and vasculogenesis. Semas are a large family of both transmembrane and secreted signaling molecules, and show subtype specific binding to different Plxn family members...
October 28, 2017: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29100074/plexin-b2-mediates-physiologic-and-pathologic-functions-of-angiogenin
#9
Wenhao Yu, Kevin A Goncalves, Shuping Li, Hiroko Kishikawa, Guangjie Sun, Hailing Yang, Nil Vanli, Yunxia Wu, Yuxiang Jiang, Miaofen G Hu, Roland H Friedel, Guo-Fu Hu
Angiogenin (ANG) is a secreted ribonuclease (RNase) with cell-type- and context-specific roles in growth, survival, and regeneration. Although these functions require receptor-mediated endocytosis and appropriate subcellular localization, the identity of the cell surface receptor remains undefined. Here, we show that plexin-B2 (PLXNB2) is the functional receptor for ANG in endothelial, cancer, neuronal, and normal hematopoietic and leukemic stem and progenitor cells. Mechanistically, PLXNB2 mediates intracellular RNA processing that contribute to cell growth, survival, and regenerative capabilities of ANG...
November 2, 2017: Cell
https://www.readbyqxmd.com/read/29095088/vegf-a121a-binding-to-neuropilins-a-concept-revisited
#10
Sarvenaz Sarabipour, Feilim Mac Gabhann
All known splice isoforms of vascular endothelial growth factor A (VEGF-A) can bind to the receptor tyrosine kinases VEGFR-1 and VEGFR-2. We focus here on VEGF-A121a and VEGF-A165a, two of the most abundant VEGF-A splice isoforms in human tissue 1 , and their ability to bind the Neuropilin co-receptors NRP1 and NRP2. The Neuropilins are key vascular, immune, and nervous system receptors on endothelial cells, neuronal axons, and regulatory T cells respectively. They serve as co-receptors for the Plexins in Semaphorin binding on neuronal and vascular endothelial cells, and for the VEGFRs in VEGF binding on vascular and lymphatic endothelial cells, and thus regulate the initiation and coordination of cell signaling by Semaphorins and VEGFs...
November 2, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/29091353/fyn-dependent-phosphorylation-of-plexina1-and-plexina2-at-conserved-tyrosines-is-essential-for-zebrafish-eye-development
#11
Riley M St Clair, Sarah E Emerson, Kristen P D'Elia, Marion E Weir, Anna M Schmoker, Alicia M Ebert, Bryan A Ballif
Plexins (Plxns) are semaphorin (Sema) receptors that play important signaling roles, particularly in the developing nervous system and vasculature. Sema-Plxn signaling regulates cellular processes such as cytoskeletal dynamics, proliferation, and differentiation. However, the receptor-proximal signaling mechanisms driving Sema-Plxn signal transduction are only partially understood. Plxn tyrosine phosphorylation is thought to play an important role in these signaling events as receptor and non-receptor tyrosine kinases have been shown to interact with Plxn receptors...
November 1, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29040270/analysis-of-the-interaction-of-plexin-b1-and-plexin-b2-with-rnd-family-proteins
#12
Thomas Wylie, Ritu Garg, Anne J Ridley, Maria R Conte
The Rnd family of proteins, Rnd1, Rnd2 and Rnd3, are atypical Rho family GTPases, which bind to but do not hydrolyse GTP. They interact with plexins, which are receptors for semaphorins, and are hypothesised to regulate plexin signalling. We recently showed that each Rnd protein has a distinct profile of interaction with three plexins, Plexin-B1, Plexin-B2 and Plexin-B3, in mammalian cells, although it is unclear which region(s) of these plexins contribute to this specificity. Here we characterise the binary interactions of the Rnd proteins with the Rho-binding domain (RBD) of Plexin-B1 and Plexin-B2 using biophysical approaches...
2017: PloS One
https://www.readbyqxmd.com/read/28973932/discovery-of-an-o-mannosylation-pathway-selectively-serving-cadherins-and-protocadherins
#13
Ida Signe Bohse Larsen, Yoshiki Narimatsu, Hiren Jitendra Joshi, Lina Siukstaite, Oliver J Harrison, Julia Brasch, Kerry M Goodman, Lars Hansen, Lawrence Shapiro, Barry Honig, Sergey Y Vakhrushev, Henrik Clausen, Adnan Halim
The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28953869/retrograde-semaphorin-plexin-signalling-drives-homeostatic-synaptic-plasticity
#14
Brian O Orr, Richard D Fetter, Graeme W Davis
Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis...
October 5, 2017: Nature
https://www.readbyqxmd.com/read/28948068/effect-of-food-intake-on-92-neurological-biomarkers-in-plasma
#15
Magnus Dencker, Ola Björgell, Joanna Hlebowicz
OBJECTIVE: This study evaluates the effect of food intake on 92 neurological biomarkers in plasma. Moreover, it investigated if any of the biomarkers were correlated with body mass index. MATERIALS AND METHODS: Twenty-two healthy subjects (11 male and 11 female aged 25.9 ± 4.2 years) were investigated. A total of 92 biomarkers were measured before a standardized meal as well as 30 and 120 min afterward with the Proseek Multiplex Neurology I kit. RESULTS: The levels for 13 biomarkers decreased significantly (p < ...
September 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28927892/cd100-plexin-b2-promotes-the-inflammation-in-psoriasis-by-activating-nf-%C3%AE%C2%BAb-and-inflammasome-in-keratinocytes
#16
Chen Zhang, Chunying Xiao, Erle Dang, Jiao Cao, Zhenlai Zhu, Meng Fu, Xu Yao, Yufeng Liu, Boquan Jin, Gang Wang, Wei Li
Plexin-B2 (PlxnB2) and its ligand, CD100 (Semaphorin 4D), are originally identified as axon-guidance molecules that function during neuronal development; however, studies also showed that CD100-Plexins participate in various immune responses. In the present study, we found that the expression of PlxnB2 on keratinocytes was specifically increased in lesional skin of psoriasis patients, but not atopic dermatitis. Levels of soluble CD100 (sCD100) and membrane CD100 (mCD100) were elevated in sera of psoriasis patients and on keratinocytes of psoriatic skin, respectively...
September 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28912336/elevated-semaphorin-5a-in-patients-with-hashimoto-s-thyroiditis-a-case-control-study
#17
Yongping Liu, Shuo Wang, Qingling Guo, Yongze Li, Jing Qin, Na Zhao, Yushu Li, Zhongyan Shan, Weiping Teng
OBJECTIVE: Hashimoto's thyroiditis (HT) is characterized by elevated specific auto-antibodies, including TgAb and TPOAb. Increasing evidence has demonstrated the essential role of Th17 cells in HT. However, the underlying mechanism is still unclear. Semaphorin 5A (Sema 5A) is involved in several autoimmune diseases through the regulation of immune cells. The aim of the present study was to explore the role of Sema 5A in HT. METHODS: We measured serum Sema 5A levels in HT (n = 92) and healthy controls (n = 111) by enzyme-linked immunosorbent assay (ELISA)...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28902178/tumor-inhibitory-effect-of-ircr201-a-novel-cross-reactive-c-met-antibody-targeting-the-psi-domain
#18
Hyunkyu Park, Donggeon Kim, Eunmi Kim, Jason K Sa, Hee Won Lee, Suji Yu, Jiwon Oh, Seok-Hyung Kim, Yeup Yoon, Do-Hyun Nam
Hepatocyte growth factor receptor (HGFR, c-Met) is an essential member of the receptor tyrosine kinase (RTK) family that is often dysregulated during tumor progression, driving a malignant phenotypic state and modulating important cellular functions including tumor growth, invasion, metastasis, and angiogenesis, providing a strong rationale for targeting HGF/c-Met signaling axis in cancer therapy. Based on its protumorigenic potentials, we developed IRCR201, a potent antagonistic antibody targeting the plexin-semaphorin-integrin (PSI) domain of c-Met, using synthetic human antibody phage libraries...
September 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28878126/endothelium-derived-extracellular-vesicles-promote-splenic-monocyte-mobilization-in-myocardial-infarction
#19
Naveed Akbar, Janet E Digby, Thomas J Cahill, Abhijeet N Tavare, Alastair L Corbin, Sushant Saluja, Sam Dawkins, Laurienne Edgar, Nadiia Rawlings, Klemen Ziberna, Eileen McNeill, Errin Johnson, Alaa A Aljabali, Rebecca A Dragovic, Mala Rohling, T Grant Belgard, Irina A Udalova, David R Greaves, Keith M Channon, Paul R Riley, Daniel C Anthony, Robin P Choudhury
Transcriptionally activated monocytes are recruited to the heart after acute myocardial infarction (AMI). After AMI in mice and humans, the number of extracellular vesicles (EVs) increased acutely. In humans, EV number correlated closely with the extent of myocardial injury. We hypothesized that EVs mediate splenic monocyte mobilization and program transcription following AMI. Some plasma EVs bear endothelial cell (EC) integrins, and both proinflammatory stimulation of ECs and AMI significantly increased VCAM-1-positive EV release...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28853092/involvement-of-semaphorin-sema4d-in-t-dependent-activation-of-b-cells
#20
Е М Kuklina, I V Nekrasova, Yu V Valieva
The involvement of endogenous semaphorin (Sema4D) into the key stage of T-dependent differentiation of B cells, formation of plasmoblasts, was demonstrated in vitro in T/B cell co-culture under conditions of polyclonal activation of T cells. The effect of semaphorin was not associated with activation of high-affinity Sema4D receptor plexin B1, but involves lowaffinity receptor CD72. These data indicate that Sema4D-dependent signal regulates not only the initial stage of B-cell activation, proliferative response to the antigen, but also further differentiation of B cells into plasma cells...
August 29, 2017: Bulletin of Experimental Biology and Medicine
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