Cytokine secretion via cholesterol-rich lipid raft-associated SNAREs at the phagocytic cup

Kay, Jason G., Murray, Rachael, Pagan, Julia K., & Stow, Jennifer (2006) Cytokine secretion via cholesterol-rich lipid raft-associated SNAREs at the phagocytic cup. Journal of Biological Chemistry, 281(17), pp. 11949-11954.

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Lipopolysaccharide-activated macrophages rapidly synthesize and secrete tumor necrosis factor α (TNFα) to prime the immune system. Surface delivery of membrane carrying newly synthesized TNFα is controlled and limited by the level of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins syntaxin 4 and SNAP-23.

Many functions in immune cells are coordinated from lipid rafts in the plasmamembrane, and we investigated a possible role for lipid rafts in TNFα trafficking and secretion. TNFα surface delivery and secretion were found to be cholesterol- dependent. Upon macrophage activation, syntaxin 4 was recruited to cholesterol-dependent lipid rafts, whereas its regulatory protein, Munc18c, was excluded from the rafts. Syntaxin 4 in activated macrophages localized to discrete cholesterol-dependent puncta on the plasmamembrane, particularly on filopodia.

Imaging the early stages of TNFα surface distribution revealed these puncta to be the initial points of TNFα delivery. During the early stages of phagocytosis, syntaxin 4 was recruited to the phagocytic cup in a cholesterol dependent manner. Insertion of VAMP3-positive recycling endosome membrane is required for efficient ingestion of a pathogen. Without this recruitment of syntaxin 4, it is not incorporated into the plasma membrane, and phagocytosis is greatly reduced. Thus, relocation of syntaxin 4 into lipid rafts in macrophages is a critical and rate-limiting step in initiating an effective immune response.

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ID Code: 50444
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website after 12 months
DOI: 10.1074/jbc.M600857200
ISSN: 0021-9258
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Enzymes (060107)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > IMMUNOLOGY (110700) > Immunology not elsewhere classified (110799)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Deposited On: 20 May 2012 23:15
Last Modified: 04 Feb 2015 05:48

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