Abstract
The extracellular vesicular compartment has emerged as a novel system of intercellular communication; however, the mechanisms involved in membrane vesicle biogenesis and secretion are as yet unclear. Among immune cells releasing membrane vesicles-mast cells that reside near tissues exposed to the environment-are master modulators of immune responses. Here, we have addressed the role of p66Shc, a novel regulator of mast cell activation and homeostasis, in the dynamic reorganization of the actin cytoskeleton that is associated with morphological changes during secretion. We show that p66Shc is recruited as a complex with the lipid phosphatase SHIP1 to the F-actin skeleton and impairs antigen-dependent cortical F-actin disassembly and membrane ruffling through the inhibition of Vav and paxillin phosphorylation. We also show that in addition to acting as a negative regulator of antigen-dependent mast cell degranulation, p66Shc limits the basal release of granule contents by inhibiting microvesicle budding from the plasma membrane and piecemeal degranulation. These findings identify p66Shc as a critical regulator of actin dynamics in mast cells, providing a basis for understanding the molecular mechanisms involved in vesicle-mediated secretion in these cells.
| Original language | English |
|---|---|
| Pages (from-to) | 285-292 |
| Number of pages | 8 |
| Journal | Journal of Leukocyte Biology |
| Volume | 95 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- Microvesicles
- SHIP1
- Signal transduction
ASJC Scopus subject areas
- Cell Biology
- Immunology
Cite this
p66Shc regulates vesicle-mediated secretion in mast cells by affecting F-actin dynamics. / Masi, Giulia; Mercati, David; Vannuccini, Elisa; Paccagnini, Eugenio; Riparbelli, Maria Giovanna; Lupetti, Pietro; Pelicci, Pier Giuseppe; Baldari, Cosima T.; Ulivieri, Cristina.
In: Journal of Leukocyte Biology, Vol. 95, No. 2, 2014, p. 285-292.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - p66Shc regulates vesicle-mediated secretion in mast cells by affecting F-actin dynamics
AU - Masi, Giulia
AU - Mercati, David
AU - Vannuccini, Elisa
AU - Paccagnini, Eugenio
AU - Riparbelli, Maria Giovanna
AU - Lupetti, Pietro
AU - Pelicci, Pier Giuseppe
AU - Baldari, Cosima T.
AU - Ulivieri, Cristina
PY - 2014
Y1 - 2014
N2 - The extracellular vesicular compartment has emerged as a novel system of intercellular communication; however, the mechanisms involved in membrane vesicle biogenesis and secretion are as yet unclear. Among immune cells releasing membrane vesicles-mast cells that reside near tissues exposed to the environment-are master modulators of immune responses. Here, we have addressed the role of p66Shc, a novel regulator of mast cell activation and homeostasis, in the dynamic reorganization of the actin cytoskeleton that is associated with morphological changes during secretion. We show that p66Shc is recruited as a complex with the lipid phosphatase SHIP1 to the F-actin skeleton and impairs antigen-dependent cortical F-actin disassembly and membrane ruffling through the inhibition of Vav and paxillin phosphorylation. We also show that in addition to acting as a negative regulator of antigen-dependent mast cell degranulation, p66Shc limits the basal release of granule contents by inhibiting microvesicle budding from the plasma membrane and piecemeal degranulation. These findings identify p66Shc as a critical regulator of actin dynamics in mast cells, providing a basis for understanding the molecular mechanisms involved in vesicle-mediated secretion in these cells.
AB - The extracellular vesicular compartment has emerged as a novel system of intercellular communication; however, the mechanisms involved in membrane vesicle biogenesis and secretion are as yet unclear. Among immune cells releasing membrane vesicles-mast cells that reside near tissues exposed to the environment-are master modulators of immune responses. Here, we have addressed the role of p66Shc, a novel regulator of mast cell activation and homeostasis, in the dynamic reorganization of the actin cytoskeleton that is associated with morphological changes during secretion. We show that p66Shc is recruited as a complex with the lipid phosphatase SHIP1 to the F-actin skeleton and impairs antigen-dependent cortical F-actin disassembly and membrane ruffling through the inhibition of Vav and paxillin phosphorylation. We also show that in addition to acting as a negative regulator of antigen-dependent mast cell degranulation, p66Shc limits the basal release of granule contents by inhibiting microvesicle budding from the plasma membrane and piecemeal degranulation. These findings identify p66Shc as a critical regulator of actin dynamics in mast cells, providing a basis for understanding the molecular mechanisms involved in vesicle-mediated secretion in these cells.
KW - Microvesicles
KW - SHIP1
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=84897027169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897027169&partnerID=8YFLogxK
U2 - 10.1189/jlb.0313178
DO - 10.1189/jlb.0313178
M3 - Article
C2 - 24078705
AN - SCOPUS:84897027169
VL - 95
SP - 285
EP - 292
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 2
ER -