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  • 1
    Publication Date: 2008-04-25
    Description: The cellular machinery promoting phagocytosis of corpses of apoptotic cells is well conserved from worms to mammals. An important component is the Caenorhabditis elegans engulfment receptor CED-1 (ref. 1) and its Drosophila orthologue, Draper. The CED-1/Draper signalling pathway is also essential for the phagocytosis of other types of 'modified self' including necrotic cells, developmentally pruned axons and dendrites, and axons undergoing Wallerian degeneration. Here we show that Drosophila Shark, a non-receptor tyrosine kinase similar to mammalian Syk and Zap-70, binds Draper through an immunoreceptor tyrosine-based activation motif (ITAM) in the Draper intracellular domain. We show that Shark activity is essential for Draper-mediated signalling events in vivo, including the recruitment of glial membranes to severed axons and the phagocytosis of axonal debris and neuronal cell corpses by glia. We also show that the Src family kinase (SFK) Src42A can markedly increase Draper phosphorylation and is essential for glial phagocytic activity. We propose that ligand-dependent Draper receptor activation initiates the Src42A-dependent tyrosine phosphorylation of Draper, the association of Shark and the activation of the Draper pathway. These Draper-Src42A-Shark interactions are strikingly similar to mammalian immunoreceptor-SFK-Syk signalling events in mammalian myeloid and lymphoid cells. Thus, Draper seems to be an ancient immunoreceptor with an extracellular domain tuned to modified self, and an intracellular domain promoting phagocytosis through an ITAM-domain-SFK-Syk-mediated signalling cascade.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493287/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493287/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ziegenfuss, Jennifer S -- Biswas, Romi -- Avery, Michelle A -- Hong, Kyoungja -- Sheehan, Amy E -- Yeung, Yee-Guide -- Stanley, E Richard -- Freeman, Marc R -- 1R01CA26504/CA/NCI NIH HHS/ -- 1R01GM55293/GM/NIGMS NIH HHS/ -- 1R01NS053538/NS/NINDS NIH HHS/ -- R37 CA026504/CA/NCI NIH HHS/ -- R37 CA026504-30/CA/NCI NIH HHS/ -- England -- Nature. 2008 Jun 12;453(7197):935-9. doi: 10.1038/nature06901. Epub 2008 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605-2324, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18432193" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Axons/metabolism/pathology ; Cell Line ; Cell Membrane/metabolism ; Central Nervous System ; Drosophila Proteins/chemistry/*metabolism ; Intracellular Signaling Peptides and Proteins/*metabolism ; Membrane Proteins/chemistry/*metabolism ; Neuroglia/*cytology ; *Phagocytosis ; Phosphorylation ; Protein Binding ; Protein Structure, Tertiary ; Protein Transport ; Protein-Tyrosine Kinases/*metabolism ; Proto-Oncogene Proteins pp60(c-src)/*metabolism ; *Signal Transduction ; Two-Hybrid System Techniques
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2009-04-03
    Description: CRM1 (also known as XPO1 and exportin 1) mediates nuclear export of hundreds of proteins through the recognition of the leucine-rich nuclear export signal (LR-NES). Here we present the 2.9 A structure of CRM1 bound to snurportin 1 (SNUPN). Snurportin 1 binds CRM1 in a bipartite manner by means of an amino-terminal LR-NES and its nucleotide-binding domain. The LR-NES is a combined alpha-helical-extended structure that occupies a hydrophobic groove between two CRM1 outer helices. The LR-NES interface explains the consensus hydrophobic pattern, preference for intervening electronegative residues and inhibition by leptomycin B. The second nuclear export signal epitope is a basic surface on the snurportin 1 nucleotide-binding domain, which binds an acidic patch on CRM1 adjacent to the LR-NES site. Multipartite recognition of individually weak nuclear export signal epitopes may be common to CRM1 substrates, enhancing CRM1 binding beyond the generally low affinity LR-NES. Similar energetic construction is also used in multipartite nuclear localization signals to provide broad substrate specificity and rapid evolution in nuclear transport.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437623/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437623/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dong, Xiuhua -- Biswas, Anindita -- Suel, Katherine E -- Jackson, Laurie K -- Martinez, Rita -- Gu, Hongmei -- Chook, Yuh Min -- 5-T32-GM008297/GM/NIGMS NIH HHS/ -- R01 GM069909/GM/NIGMS NIH HHS/ -- R01GM069909/GM/NIGMS NIH HHS/ -- R01GM069909-03S1/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1136-41. doi: 10.1038/nature07975. Epub 2009 Apr 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park, Dallas, Texas 75390-9041, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19339969" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Crystallography, X-Ray ; Epitopes ; Fatty Acids, Unsaturated/pharmacology ; Humans ; Hydrophobic and Hydrophilic Interactions ; Karyopherins/*chemistry/*metabolism ; Leucine/*metabolism ; Models, Molecular ; Nuclear Export Signals/*physiology ; Protein Binding/drug effects ; Protein Conformation ; Receptors, Cytoplasmic and Nuclear/*chemistry/*metabolism ; Structure-Activity Relationship ; Substrate Specificity ; snRNP Core Proteins/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2009-08-21
    Description: A stochastic background of gravitational waves is expected to arise from a superposition of a large number of unresolved gravitational-wave sources of astrophysical and cosmological origin. It should carry unique signatures from the earliest epochs in the evolution of the Universe, inaccessible to standard astrophysical observations. Direct measurements of the amplitude of this background are therefore of fundamental importance for understanding the evolution of the Universe when it was younger than one minute. Here we report limits on the amplitude of the stochastic gravitational-wave background using the data from a two-year science run of the Laser Interferometer Gravitational-wave Observatory (LIGO). Our result constrains the energy density of the stochastic gravitational-wave background normalized by the critical energy density of the Universe, in the frequency band around 100 Hz, to be 〈6.9 x 10(-6) at 95% confidence. The data rule out models of early Universe evolution with relatively large equation-of-state parameter, as well as cosmic (super)string models with relatively small string tension that are favoured in some string theory models. This search for the stochastic background improves on the indirect limits from Big Bang nucleosynthesis and cosmic microwave background at 100 Hz.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉LIGO Scientific Collaboration & Virgo Collaboration -- Abbott, B P -- Abbott, R -- Acernese, F -- Adhikari, R -- Ajith, P -- Allen, B -- Allen, G -- Alshourbagy, M -- Amin, R S -- Anderson, S B -- Anderson, W G -- Antonucci, F -- Aoudia, S -- Arain, M A -- Araya, M -- Armandula, H -- Armor, P -- Arun, K G -- Aso, Y -- Aston, S -- Astone, P -- Aufmuth, P -- Aulbert, C -- Babak, S -- Baker, P -- Ballardin, G -- Ballmer, S -- Barker, C -- Barker, D -- Barone, F -- Barr, B -- Barriga, P -- Barsotti, L -- Barsuglia, M -- Barton, M A -- Bartos, I -- Bassiri, R -- Bastarrika, M -- Bauer, Th S -- Behnke, B -- Beker, M -- Benacquista, M -- Betzwieser, J -- Beyersdorf, P T -- Bigotta, S -- Bilenko, I A -- Billingsley, G -- Birindelli, S -- Biswas, R -- Bizouard, M A -- Black, E -- Blackburn, J K -- Blackburn, L -- Blair, D -- Bland, B -- Boccara, C -- Bodiya, T P -- Bogue, L -- Bondu, F -- Bonelli, L -- Bork, R -- Boschi, V -- Bose, S -- Bosi, L -- Braccini, S -- Bradaschia, C -- Brady, P R -- Braginsky, V B -- Brand, J F J van den -- Brau, J E -- Bridges, D O -- Brillet, A -- Brinkmann, M -- Brisson, V -- Van Den Broeck, C -- Brooks, A F -- Brown, D A -- Brummit, A -- Brunet, G -- Bullington, A -- Bulten, H J -- Buonanno, A -- Burmeister, O -- Buskulic, D -- Byer, R L -- Cadonati, L -- Cagnoli, G -- Calloni, E -- Camp, J B -- Campagna, E -- Cannizzo, J -- Cannon, K C -- Canuel, B -- Cao, J -- Carbognani, F -- Cardenas, L -- Caride, S -- Castaldi, G -- Caudill, S -- Cavaglia, M -- Cavalier, F -- Cavalieri, R -- Cella, G -- Cepeda, C -- Cesarini, E -- Chalermsongsak, T -- Chalkley, E -- Charlton, P -- Chassande-Mottin, E -- Chatterji, S -- Chelkowski, S -- Chen, Y -- Christensen, N -- Chung, C T Y -- Clark, D -- Clark, J -- Clayton, J H -- Cleva, F -- Coccia, E -- Cokelaer, T -- Colacino, C N -- Colas, J -- Colla, A -- Colombini, M -- Conte, R -- Cook, D -- Corbitt, T R C -- Corda, C -- Cornish, N -- Corsi, A -- Coulon, J-P -- Coward, D -- Coyne, D C -- Creighton, J D E -- Creighton, T D -- Cruise, A M -- Culter, R M -- Cumming, A -- Cunningham, L -- Cuoco, E -- Danilishin, S L -- D'Antonio, S -- Danzmann, K -- Dari, A -- Dattilo, V -- Daudert, B -- Davier, M -- Davies, G -- Daw, E J -- Day, R -- De Rosa, R -- Debra, D -- Degallaix, J -- Del Prete, M -- Dergachev, V -- Desai, S -- Desalvo, R -- Dhurandhar, S -- Di Fiore, L -- Di Lieto, A -- Di Paolo Emilio, M -- Di Virgilio, A -- Diaz, M -- Dietz, A -- Donovan, F -- Dooley, K L -- Doomes, E E -- Drago, M -- Drever, R W P -- Dueck, J -- Duke, I -- Dumas, J-C -- Dwyer, J G -- Echols, C -- Edgar, M -- Effler, A -- Ehrens, P -- Ely, G -- Espinoza, E -- Etzel, T -- Evans, M -- Evans, T -- Fafone, V -- Fairhurst, S -- Faltas, Y -- Fan, Y -- Fazi, D -- Fehrmann, H -- Ferrante, I -- Fidecaro, F -- Finn, L S -- Fiori, I -- Flaminio, R -- Flasch, K -- Foley, S -- Forrest, C -- Fotopoulos, N -- Fournier, J-D -- Franc, J -- Franzen, A -- Frasca, S -- Frasconi, F -- Frede, M -- Frei, M -- Frei, Z -- Freise, A -- Frey, R -- Fricke, T -- Fritschel, P -- Frolov, V V -- Fyffe, M -- Galdi, V -- Gammaitoni, L -- Garofoli, J A -- Garufi, F -- Genin, E -- Gennai, A -- Gholami, I -- Giaime, J A -- Giampanis, S -- Giardina, K D -- Giazotto, A -- Goda, K -- Goetz, E -- Goggin, L M -- Gonzalez, G -- Gorodetsky, M L -- Gobler, S -- Gouaty, R -- Granata, M -- Granata, V -- Grant, A -- Gras, S -- Gray, C -- Gray, M -- Greenhalgh, R J S -- Gretarsson, A M -- Greverie, C -- Grimaldi, F -- Grosso, R -- Grote, H -- Grunewald, S -- Guenther, M -- Guidi, G -- Gustafson, E K -- Gustafson, R -- Hage, B -- Hallam, J M -- Hammer, D -- Hammond, G D -- Hanna, C -- Hanson, J -- Harms, J -- Harry, G M -- Harry, I W -- Harstad, E D -- Haughian, K -- Hayama, K -- Heefner, J -- Heitmann, H -- Hello, P -- Heng, I S -- Heptonstall, A -- Hewitson, M -- Hild, S -- Hirose, E -- Hoak, D -- Hodge, K A -- Holt, K -- Hosken, D J -- Hough, J -- Hoyland, D -- Huet, D -- Hughey, B -- Huttner, S H -- Ingram, D R -- Isogai, T -- Ito, M -- Ivanov, A -- Johnson, B -- Johnson, W W -- Jones, D I -- Jones, G -- Jones, R -- Sancho de la Jordana, L -- Ju, L -- Kalmus, P -- Kalogera, V -- Kandhasamy, S -- Kanner, J -- Kasprzyk, D -- Katsavounidis, E -- Kawabe, K -- Kawamura, S -- Kawazoe, F -- Kells, W -- Keppel, D G -- Khalaidovski, A -- Khalili, F Y -- Khan, R -- Khazanov, E -- King, P -- Kissel, J S -- Klimenko, S -- Kokeyama, K -- Kondrashov, V -- Kopparapu, R -- Koranda, S -- Kozak, D -- Krishnan, B -- Kumar, R -- Kwee, P -- La Penna, P -- Lam, P K -- Landry, M -- Lantz, B -- Laval, M -- Lazzarini, A -- Lei, H -- Lei, M -- Leindecker, N -- Leonor, I -- Leroy, N -- Letendre, N -- Li, C -- Lin, H -- Lindquist, P E -- Littenberg, T B -- Lockerbie, N A -- Lodhia, D -- Longo, M -- Lorenzini, M -- Loriette, V -- Lormand, M -- Losurdo, G -- Lu, P -- Lubinski, M -- Lucianetti, A -- Luck, H -- Machenschalk, B -- Macinnis, M -- Mackowski, J-M -- Mageswaran, M -- Mailand, K -- Majorana, E -- Man, N -- Mandel, I -- Mandic, V -- Mantovani, M -- Marchesoni, F -- Marion, F -- Marka, S -- Marka, Z -- Markosyan, A -- Markowitz, J -- Maros, E -- Marque, J -- Martelli, F -- Martin, I W -- Martin, R M -- Marx, J N -- Mason, K -- Masserot, A -- Matichard, F -- Matone, L -- Matzner, R A -- Mavalvala, N -- McCarthy, R -- McClelland, D E -- McGuire, S C -- McHugh, M -- McIntyre, G -- McKechan, D J A -- McKenzie, K -- Mehmet, M -- Melatos, A -- Melissinos, A C -- Mendell, G -- Menendez, D F -- Menzinger, F -- Mercer, R A -- Meshkov, S -- Messenger, C -- Meyer, M S -- Michel, C -- Milano, L -- Miller, J -- Minelli, J -- Minenkov, Y -- Mino, Y -- Mitrofanov, V P -- Mitselmakher, G -- Mittleman, R -- Miyakawa, O -- Moe, B -- Mohan, M -- Mohanty, S D -- Mohapatra, S R P -- Moreau, J -- Moreno, G -- Morgado, N -- Morgia, A -- Morioka, T -- Mors, K -- Mosca, S -- Mossavi, K -- Mours, B -- Mowlowry, C -- Mueller, G -- Muhammad, D -- Muhlen, H Zur -- Mukherjee, S -- Mukhopadhyay, H -- Mullavey, A -- Muller-Ebhardt, H -- Munch, J -- Murray, P G -- Myers, E -- Myers, J -- Nash, T -- Nelson, J -- Neri, I -- Newton, G -- Nishizawa, A -- Nocera, F -- Numata, K -- Ochsner, E -- O'Dell, J -- Ogin, G H -- O'Reilly, B -- O'Shaughnessy, R -- Ottaway, D J -- Ottens, R S -- Overmier, H -- Owen, B J -- Pagliaroli, G -- Palomba, C -- Pan, Y -- Pankow, C -- Paoletti, F -- Papa, M A -- Parameshwaraiah, V -- Pardi, S -- Pasqualetti, A -- Passaquieti, R -- Passuello, D -- Patel, P -- Pedraza, M -- Penn, S -- Perreca, A -- Persichetti, G -- Pichot, M -- Piergiovanni, F -- Pierro, V -- Pinard, L -- Pinto, I M -- Pitkin, M -- Pletsch, H J -- Plissi, M V -- Poggiani, R -- Postiglione, F -- Principe, M -- Prix, R -- Prodi, G A -- Prokhorov, L -- Punken, O -- Punturo, M -- Puppo, P -- Putten, S van der -- Quetschke, V -- Raab, F J -- Rabaste, O -- Rabeling, D S -- Radkins, H -- Raffai, P -- Raics, Z -- Rainer, N -- Rakhmanov, M -- Rapagnani, P -- Raymond, V -- Re, V -- Reed, C M -- Reed, T -- Regimbau, T -- Rehbein, H -- Reid, S -- Reitze, D H -- Ricci, F -- Riesen, R -- Riles, K -- Rivera, B -- Roberts, P -- Robertson, N A -- Robinet, F -- Robinson, C -- Robinson, E L -- Rocchi, A -- Roddy, S -- Rolland, L -- Rollins, J -- Romano, J D -- Romano, R -- Romie, J H -- Rover, C -- Rowan, S -- Rudiger, A -- Ruggi, P -- Russell, P -- Ryan, K -- Sakata, S -- Salemi, F -- Sandberg, V -- Sannibale, V -- Santamaria, L -- Saraf, S -- Sarin, P -- Sassolas, B -- Sathyaprakash, B S -- Sato, S -- Satterthwaite, M -- Saulson, P R -- Savage, R -- Savov, P -- Scanlan, M -- Schilling, R -- Schnabel, R -- Schofield, R -- Schulz, B -- Schutz, B F -- Schwinberg, P -- Scott, J -- Scott, S M -- Searle, A C -- Sears, B -- Seifert, F -- Sellers, D -- Sengupta, A S -- Sentenac, D -- Sergeev, A -- Shapiro, B -- Shawhan, P -- Shoemaker, D H -- Sibley, A -- Siemens, X -- Sigg, D -- Sinha, S -- Sintes, A M -- Slagmolen, B J J -- Slutsky, J -- van der Sluys, M V -- Smith, J R -- Smith, M R -- Smith, N D -- Somiya, K -- Sorazu, B -- Stein, A -- Stein, L C -- Steplewski, S -- Stochino, A -- Stone, R -- Strain, K A -- Strigin, S -- Stroeer, A -- Sturani, R -- Stuver, A L -- Summerscales, T Z -- Sun, K-X -- Sung, M -- Sutton, P J -- Swinkels, B L -- Szokoly, G P -- Talukder, D -- Tang, L -- Tanner, D B -- Tarabrin, S P -- Taylor, J R -- Taylor, R -- Terenzi, R -- Thacker, J -- Thorne, K A -- Thorne, K S -- Thuring, A -- Tokmakov, K V -- Toncelli, A -- Tonelli, M -- Torres, C -- Torrie, C -- Tournefier, E -- Travasso, F -- Traylor, G -- Trias, M -- Trummer, J -- Ugolini, D -- Ulmen, J -- Urbanek, K -- Vahlbruch, H -- Vajente, G -- Vallisneri, M -- Vass, S -- Vaulin, R -- Vavoulidis, M -- Vecchio, A -- Vedovato, G -- van Veggel, A A -- Veitch, J -- Veitch, P -- Veltkamp, C -- Verkindt, D -- Vetrano, F -- Vicere, A -- Villar, A -- Vinet, J-Y -- Vocca, H -- Vorvick, C -- Vyachanin, S P -- Waldman, S J -- Wallace, L -- Ward, H -- Ward, R L -- Was, M -- Weidner, A -- Weinert, M -- Weinstein, A J -- Weiss, R -- Wen, L -- Wen, S -- Wette, K -- Whelan, J T -- Whitcomb, S E -- Whiting, B F -- Wilkinson, C -- Willems, P A -- Williams, H R -- Williams, L -- Willke, B -- Wilmut, I -- Winkelmann, L -- Winkler, W -- Wipf, C C -- Wiseman, A G -- Woan, G -- Wooley, R -- Worden, J -- Wu, W -- Yakushin, I -- Yamamoto, H -- Yan, Z -- Yoshida, S -- Yvert, M -- Zanolin, M -- Zhang, J -- Zhang, L -- Zhao, C -- Zotov, N -- Zucker, M E -- Zweizig, J -- England -- Nature. 2009 Aug 20;460(7258):990-4. doi: 10.1038/nature08278.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lists of participants and their affiliations appear at the end of the paper.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693079" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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