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The SNARE Machinery in Mast Cell Secretion.

Lorentz A, Baumann A, Vitte J, Blank U - Front Immunol (2012)

Bottom Line: During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines.Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis.In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Medicine, University of Hohenheim Stuttgart, Germany.

ABSTRACT
Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

No MeSH data available.


Related in: MedlinePlus

SNARE catalyzed granule fusion in mast cells. (A) Secretion of mediators requires fusion of vesicle and plasma membranes. Upon activation through FcεRI secretory granules translocate to and dock at the plasma membrane where the t-SNAREs SNAP-23 and STX4 together with the v-SNARE VAMP8 form stable tetrameric complexes of bundled helices bringing the lipid bilayers into a close distance to catalyze membrane fusion. The SNARE motifs of SNAP-23, STX4, and VAMP8, which become highly organized in the four helical bundle during the formation of the trans-SNARE complex are highlighted in color. (B) The primary structure of human SNAP-23, STX4, and VAMP8 as adapted from Hong (2005) is shown with SNARE motifs for each protein in like colors. STX4 and VAMP8 have C-terminal transmembrane domains (TM), whereas the linker domain of SNAP-23, which connects the two SNARE motifs, has a membrane anchor domain, consisting of palmitoylated cysteine residues (M). Numbers indicate protein or domain boundaries, arrows indicate potential phosphorylation sites (http://www.phosphosite.org). Phosphorylation of mouse SNAP-23 on Ser95 and Ser120 was found to modulate regulated mast cell exocytosis (Hepp et al., 2005), whereas phosphorylation of STX4 was not altered during secretion in RBL cells (Pombo et al., 2001).
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Figure 2: SNARE catalyzed granule fusion in mast cells. (A) Secretion of mediators requires fusion of vesicle and plasma membranes. Upon activation through FcεRI secretory granules translocate to and dock at the plasma membrane where the t-SNAREs SNAP-23 and STX4 together with the v-SNARE VAMP8 form stable tetrameric complexes of bundled helices bringing the lipid bilayers into a close distance to catalyze membrane fusion. The SNARE motifs of SNAP-23, STX4, and VAMP8, which become highly organized in the four helical bundle during the formation of the trans-SNARE complex are highlighted in color. (B) The primary structure of human SNAP-23, STX4, and VAMP8 as adapted from Hong (2005) is shown with SNARE motifs for each protein in like colors. STX4 and VAMP8 have C-terminal transmembrane domains (TM), whereas the linker domain of SNAP-23, which connects the two SNARE motifs, has a membrane anchor domain, consisting of palmitoylated cysteine residues (M). Numbers indicate protein or domain boundaries, arrows indicate potential phosphorylation sites (http://www.phosphosite.org). Phosphorylation of mouse SNAP-23 on Ser95 and Ser120 was found to modulate regulated mast cell exocytosis (Hepp et al., 2005), whereas phosphorylation of STX4 was not altered during secretion in RBL cells (Pombo et al., 2001).

Mentions: The fusion between vesicles or the plasma membrane is not a spontaneous event. It requires a specific set of proteins called Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) that are highly conserved in all eukaryotes (Sudhof and Rothman, 2009; Sudhof and Rizo, 2011). They were initially discovered by several independent approaches involving yeast genetics and biochemical purification procedures from synaptic membranes and by the ability to bind soluble N-ethylmaleimide-sensitive factor (NSF)-attachment proteins, which are adapters that connect the fusion machinery to the NSF ATPase (Novick et al., 1980; Bennett and Scheller, 1993; Sollner et al., 1993). The SNARE machinery of membrane fusion involves different sets of proteins that lie on opposing membranes. They enable fusion by forming a highly stable tetrameric trans-SNARE complex through four conserved 60–70 aa SNARE motifs (Sutton et al., 1998). Dissociation of this complex is the energy-requiring step in fusion and is mediated by the NSF ATPase (Hanson et al., 1997). A typical trans-SNARE complex at the plasma membrane includes a vesicular SNARE (v-SNARE) such as vesicle associated membrane protein (VAMP) that pairs with two target membrane SNAREs (t-SNAREs) such as a Syntaxin (STX) molecule and synaptosome-associated protein of 23 (ubiquitous) or 25 (neuronal) kDa (SNAP-23/25) containing two SNARE motifs (Sutton et al., 1998). To take into account that v-SNAREs can also be found on the target membrane, for example in the case of homotypic vesicle fusion, SNAREs have also been classified structurally into R-SNAREs (corresponding with few exceptions to v-SNAREs) based on a central R residue in the 0 layer of the classical four-helix-bundle of the SNARE complex and Q-SNAREs with a central Q residue (Hong, 2005). Trans-SNARE complex, generally consists of either one v-SNARE and two or three t-SNAREs or one R-SNARE and two or three Q-SNAREs. Figure 2A illustrates SNARE complex formation catalyzing granule fusion in mast cells and Figure 2B shows the domain structure of these SNAREs and potential phosphorylation sites.


The SNARE Machinery in Mast Cell Secretion.

Lorentz A, Baumann A, Vitte J, Blank U - Front Immunol (2012)

SNARE catalyzed granule fusion in mast cells. (A) Secretion of mediators requires fusion of vesicle and plasma membranes. Upon activation through FcεRI secretory granules translocate to and dock at the plasma membrane where the t-SNAREs SNAP-23 and STX4 together with the v-SNARE VAMP8 form stable tetrameric complexes of bundled helices bringing the lipid bilayers into a close distance to catalyze membrane fusion. The SNARE motifs of SNAP-23, STX4, and VAMP8, which become highly organized in the four helical bundle during the formation of the trans-SNARE complex are highlighted in color. (B) The primary structure of human SNAP-23, STX4, and VAMP8 as adapted from Hong (2005) is shown with SNARE motifs for each protein in like colors. STX4 and VAMP8 have C-terminal transmembrane domains (TM), whereas the linker domain of SNAP-23, which connects the two SNARE motifs, has a membrane anchor domain, consisting of palmitoylated cysteine residues (M). Numbers indicate protein or domain boundaries, arrows indicate potential phosphorylation sites (http://www.phosphosite.org). Phosphorylation of mouse SNAP-23 on Ser95 and Ser120 was found to modulate regulated mast cell exocytosis (Hepp et al., 2005), whereas phosphorylation of STX4 was not altered during secretion in RBL cells (Pombo et al., 2001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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Figure 2: SNARE catalyzed granule fusion in mast cells. (A) Secretion of mediators requires fusion of vesicle and plasma membranes. Upon activation through FcεRI secretory granules translocate to and dock at the plasma membrane where the t-SNAREs SNAP-23 and STX4 together with the v-SNARE VAMP8 form stable tetrameric complexes of bundled helices bringing the lipid bilayers into a close distance to catalyze membrane fusion. The SNARE motifs of SNAP-23, STX4, and VAMP8, which become highly organized in the four helical bundle during the formation of the trans-SNARE complex are highlighted in color. (B) The primary structure of human SNAP-23, STX4, and VAMP8 as adapted from Hong (2005) is shown with SNARE motifs for each protein in like colors. STX4 and VAMP8 have C-terminal transmembrane domains (TM), whereas the linker domain of SNAP-23, which connects the two SNARE motifs, has a membrane anchor domain, consisting of palmitoylated cysteine residues (M). Numbers indicate protein or domain boundaries, arrows indicate potential phosphorylation sites (http://www.phosphosite.org). Phosphorylation of mouse SNAP-23 on Ser95 and Ser120 was found to modulate regulated mast cell exocytosis (Hepp et al., 2005), whereas phosphorylation of STX4 was not altered during secretion in RBL cells (Pombo et al., 2001).
Mentions: The fusion between vesicles or the plasma membrane is not a spontaneous event. It requires a specific set of proteins called Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) that are highly conserved in all eukaryotes (Sudhof and Rothman, 2009; Sudhof and Rizo, 2011). They were initially discovered by several independent approaches involving yeast genetics and biochemical purification procedures from synaptic membranes and by the ability to bind soluble N-ethylmaleimide-sensitive factor (NSF)-attachment proteins, which are adapters that connect the fusion machinery to the NSF ATPase (Novick et al., 1980; Bennett and Scheller, 1993; Sollner et al., 1993). The SNARE machinery of membrane fusion involves different sets of proteins that lie on opposing membranes. They enable fusion by forming a highly stable tetrameric trans-SNARE complex through four conserved 60–70 aa SNARE motifs (Sutton et al., 1998). Dissociation of this complex is the energy-requiring step in fusion and is mediated by the NSF ATPase (Hanson et al., 1997). A typical trans-SNARE complex at the plasma membrane includes a vesicular SNARE (v-SNARE) such as vesicle associated membrane protein (VAMP) that pairs with two target membrane SNAREs (t-SNAREs) such as a Syntaxin (STX) molecule and synaptosome-associated protein of 23 (ubiquitous) or 25 (neuronal) kDa (SNAP-23/25) containing two SNARE motifs (Sutton et al., 1998). To take into account that v-SNAREs can also be found on the target membrane, for example in the case of homotypic vesicle fusion, SNAREs have also been classified structurally into R-SNAREs (corresponding with few exceptions to v-SNAREs) based on a central R residue in the 0 layer of the classical four-helix-bundle of the SNARE complex and Q-SNAREs with a central Q residue (Hong, 2005). Trans-SNARE complex, generally consists of either one v-SNARE and two or three t-SNAREs or one R-SNARE and two or three Q-SNAREs. Figure 2A illustrates SNARE complex formation catalyzing granule fusion in mast cells and Figure 2B shows the domain structure of these SNAREs and potential phosphorylation sites.

Bottom Line: During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines.Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis.In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

View Article: PubMed Central - PubMed

Affiliation: Department of Nutritional Medicine, University of Hohenheim Stuttgart, Germany.

ABSTRACT
Mast cells are known as inflammatory cells which exert their functions in allergic and anaphylactic reactions by secretion of numerous inflammatory mediators. During an allergic response, the high-affinity IgE receptor, FcεRI, becomes cross-linked by receptor-bound IgE and antigen resulting in immediate release of pre-synthesized mediators - stored in granules - as well as in de novo synthesis of various mediators like cytokines and chemokines. Soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNARE) proteins were found to play a central role in regulating membrane fusion events during exocytosis. In addition, several accessory regulators like Munc13, Munc18, Rab GTPases, secretory carrier membrane proteins, complexins, or synaptotagmins were found to be involved in membrane fusion. In this review we summarize our current knowledge about the SNARE machinery and its mechanism of action in mast cell secretion.

No MeSH data available.


Related in: MedlinePlus