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36 Exocytosis of large cargo: a lesson from coronaviruses Carolyn Machamer 1 , Travis Ruch 1 . Johns Hopkins University School of Medicine, Baltimore MD 21205 1 Abstract: Coronaviruses are an interesting model for studying exocytosis of large cargo. These enveloped viruses assemble by budding into the lumen of the ER-Golgi intermediate compartment, and are released by exocytosis. However, the virions (~100 nm) are larger than the typical secretory vesicle. How do cells handle this large cargo? We have evidence that one of the viral envelope proteins, E, modifies the microenvironment of the Golgi complex to enhance release of infectious virus. The E protein helps orchestrate budding and is incorporated into the virus envelope at low levels, but is made in excess infected cells and is thought to have additional functions. E is a small protein with a single hydrophobic domain, and has ion channel activity in vitro when inserted into planar bilayers. To test the role of the potential ion channel function, we constructed a recombinant coronavirus containing E protein with a heterologous hydrophobic domain. The mutant virus assembles normally, but release of infectious virus is severely compromised. Virions accumulate intracellularly in vacuolar structures where partial proteolysis leads to release of non-infectious particles. When overexpressed from cDNA, the coronavirus E protein induces morphological changes in the Golgi complex and alters cargo traffic. There are two critical residues in the hydrophobic domain required for these effects, suggesting that ion channel function may be critical for productive exocytosis of infectious virions. Elucidation of the mechanism by which the E protein promotes the release of infectious virions should help dissect the process by which cells handle other large cargo.
37 Mechanism of secretory cargo sorting at the TGN Vivek Malhotra 1 CRG: Center for Genomic Regulation, Barcelon 08003, Spain 1 Abstract: Knockdown of actin severing protein Cofilin by siRNA and, over expression of inactive Cofilin or Cofilin-inactivating kinase (LIMK), arrested secretion of an exogenously expressed soluble secretory protein in the Trans Golgi Network (TGN) of mammalian cells. A SILAC-mass spectrometry based protein profiling revealed that a large number of endogenous secretory proteins were not secreted under these conditions. Surprisingly, a population of proteins normally retained in the Golgi was secreted. There was a similar defect in the delivery of integral membrane proteins to the cell surface. Overall, these findings indicate defective cargo sorting at the TGN. We suggest that Cofilin dependent actin trimming generates a sorting domain at the TGN, which filters secretory cargo for export; uncontrolled growth of this domain traps proteins not destined for secretion and excludes secretory proteins. I will present new data on the downstream effectors of Cofilin that are required for secretory cargo sorting at the TGN.
Page 1 and 2: October 28 - October 31, 2010 Bioch
Page 3 and 4: Symposium Agenda Thursday, October
Page 5 and 6: 12:10 p.m. - 4:00 p.m. Lunch and Fr
Page 7 and 8: 4:50 p.m. - 5:00 p.m. Discussion 5:
Page 9 and 10: Poster Presentations Last Names A -
Page 11 and 12: The Role of Ceroid Lipofuscinosis N
Page 13 and 14: A novel Golgi-localized protein inv
Page 15 and 16: 2 The dynamics of SNARE complexes i
Page 17 and 18: 4 Significant divergence in mammali
Page 19 and 20: 6 The Tumoricidal Action of the Ade
Page 21 and 22: 8 LMTK2 Regulates CFTR Recycling in
Page 23 and 24: 10 Sorting in the Golgi Apparatus C
Page 25 and 26: 12 Negative regulation of the endoc
Page 27 and 28: 14 Mechanistic details of sorting n
Page 29 and 30: 16 An ESCRTs View of Receptor Endoc
Page 31 and 32: 18 GOLPH3 Bridges PtdIns(4)P and My
Page 33 and 34: 20 Novel fluorescent probes to stud
Page 35 and 36: 22 Regulation of Ligand-Independent
Page 37 and 38: 24 A Fifth Adaptor Protein Complex
Page 39 and 40: 26 CATCHR-Family Tethering Complexe
Page 41 and 42: 28 Rab7 localization and activity a
Page 43 and 44: 30 The Drosophila Golgi transmembra
Page 45 and 46: 33 Cbl Amino Acids at a Putative Di
Page 47: 35 The role of COG subcomplexes in
Page 51 and 52: 39 Understanding the mechanism of G
Page 53 and 54: 41 Mechanisms for selective activat
Page 55 and 56: 44 A novel coat complex traffics me
Page 57 and 58: 46 Membrane trafficking in cytokine
Page 59 and 60: 48 Phosphatidylinositol 4-phosphate
Page 61 and 62: 50 Control of Golgi function by Rab
Page 63 and 64: 52 Adenosine mediated modulation of
Page 65 and 66: 54 Syp1 regulation of actin polymer
Page 67 and 68: 56 Rap1A: A Novel Interactor Involv
Page 69 and 70: 58 Ctage5 is involved in the endopl
Page 71 and 72: 60 A vesicle carrier that mediates
Page 73 and 74: 62 Structural Insights into Dynamin
Page 75 and 76: 64 Identification and interaction m
Page 77 and 78: 66 hRME-6, a rab5GEF that integrate
Page 79 and 80: 68 Assembly of caveolin-1 and cavin
Page 81 and 82: 70 Opposing roles of Annexin A1 and
Page 83 and 84: 72 The role of SNX-BAR proteins in
Page 85 and 86: 74 TRAPP is required for ER exit of
Page 87 and 88: 76 A structural analysis of the ER
Page 89 and 90: 78 Cell cycle-regulated Golgi stack
Page 91 and 92: 80 Rab 14 regulates tight junction
Page 93 and 94: 82 Dissecting the roles of O-glycos
Page 95 and 96: Author Index - A- Abay, S., 33 Acha
Page 97 and 98: Marsico, G., 83 Mattera, R., 11 Max
Page 99:
2011 ASBMB Special Symposia Series
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