HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data Supplemental Data All Versions of this Article: M600365-MCP200v1 6/5/767    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Glossary Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Casey, T. M. Articles by Hewitt, E. W. Search for Related Content PubMed PubMed Citation Articles by Casey, T. M. Articles by Hewitt, E. W. Social Bookmarking                      What's this?

Molecular & Cellular Proteomics 6:767-780, 2007.
© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Research

Organelle Proteomics

Identification of the Exocytic Machinery Associated with the Natural Killer Cell Secretory Lysosome^*,S

Tammy M. Casey, Josephine L. Meade and Eric W. Hewitt^,¶

From the Institute of Molecular and Cellular Biology, Garstang Building, University of Leeds, Leeds LS2 9JT, United Kingdom and Leeds Institute of Molecular Medicine, University of Leeds, St. James University Hospital, Leeds LS9 7TF, United Kingdom

Natural killer (NK) cells and cytotoxic T lymphocytes eliminate virally infected and transformed cells. Target cell killing is mediated by the regulated exocytosis of secretory lysosomes, which deliver perforin and proapoptotic granzymes to the infected or transformed cell. Yet despite the central role that secretory lysosome exocytosis plays in the immune response to viruses and tumors, little is known about the molecular machinery that regulates the docking and fusion of this organelle with the plasma membrane. To identify potential components of this exocytic machinery we used proteomics to define the protein composition of the NK cell secretory lysosome membrane. Secretory lysosomes were isolated from the NK cell line YTS by subcellular fractionation, integral membrane proteins and membrane-associated proteins were enriched using Triton X-114 and separated by SDS-PAGE, and tryptic peptides were identified by LC ESI-MS/MS. In total 221 proteins were identified unambiguously in the secretory lysosome membrane fraction of which 61% were predicted to be either integral membrane proteins or membrane-associated proteins. A significant proportion of the proteins identified play a role in vesicular trafficking, including members of both the Rab GTPase and soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) and protein families. These proteins include Rab27a and the SNARE vesicle-associated membrane protein-7, both of which were enriched in the secretory lysosome fraction and represent potential components of the machinery that regulates the exocytosis of this organelle in NK cells.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Z. Cao, C. Li, J. N. Higginbotham, J. L. Franklin, D. L. Tabb, R. Graves-Deal, S. Hill, K. Cheek, W. G. Jerome, L. A. Lapierre, et al. Use of Fluorescence-activated Vesicle Sorting for Isolation of Naked2-associated, Basolaterally Targeted Exocytic Vesicles for Proteomics Analysis Mol. Cell. Proteomics, September 1, 2008; 7(9): 1651 - 1667. [Abstract] [Full Text] [PDF]

				S. M. Uriarte, D. W. Powell, G. C. Luerman, M. L. Merchant, T. D. Cummins, N. R. Jog, R. A. Ward, and K. R. McLeish Comparison of Proteins Expressed on Secretory Vesicle Membranes and Plasma Membranes of Human Neutrophils J. Immunol., April 15, 2008; 180(8): 5575 - 5581. [Abstract] [Full Text] [PDF]

				G. B. Scott, J. L. Meade, and G. P. Cook Profiling killers; unravelling the pathways of human natural killer cell function Brief Funct Genomic Proteomic, January 21, 2008; (2008) elm037v1. [Abstract] [Full Text] [PDF]