p66Shc regulates vesicle-mediated secretion in mast cells by affecting F-actin dynamics

Giulia Masi, David Mercati, Elisa Vannuccini, Eugenio Paccagnini, Maria Giovanna Riparbelli, Pietro Lupetti, Pier Giuseppe Pelicci, Cosima T. Baldari, Cristina Ulivieri

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)285-292
Number of pages8
JournalJournal of Leukocyte Biology
Volume95
Issue number2
DOIs
Publication statusPublished - 2014

Fingerprint

Mast Cells
Actins
Cell Membrane
Paxillin
Antigens
Cell Degranulation
Membranes
Actin Cytoskeleton
Phosphoric Monoester Hydrolases
Skeleton
Homeostasis
Phosphorylation
Lipids

Keywords

  • Microvesicles
  • SHIP1
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Masi, G., Mercati, D., Vannuccini, E., Paccagnini, E., Riparbelli, M. G., Lupetti, P., ... Ulivieri, C. (2014). p66Shc regulates vesicle-mediated secretion in mast cells by affecting F-actin dynamics. Journal of Leukocyte Biology, 95(2), 285-292. https://doi.org/10.1189/jlb.0313178

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 journalArticle

Masi, G, Mercati, D, Vannuccini, E, Paccagnini, E, Riparbelli, MG, Lupetti, P, Pelicci, PG, Baldari, CT & Ulivieri, C 2014, 'p66Shc regulates vesicle-mediated secretion in mast cells by affecting F-actin dynamics', Journal of Leukocyte Biology, vol. 95, no. 2, pp. 285-292. https://doi.org/10.1189/jlb.0313178
Masi G, Mercati D, Vannuccini E, Paccagnini E, Riparbelli MG, Lupetti P et al. p66Shc regulates vesicle-mediated secretion in mast cells by affecting F-actin dynamics. Journal of Leukocyte Biology. 2014;95(2):285-292. https://doi.org/10.1189/jlb.0313178
Masi, Giulia ; Mercati, David ; Vannuccini, Elisa ; Paccagnini, Eugenio ; Riparbelli, Maria Giovanna ; Lupetti, Pietro ; Pelicci, Pier Giuseppe ; Baldari, Cosima T. ; Ulivieri, Cristina. / p66Shc regulates vesicle-mediated secretion in mast cells by affecting F-actin dynamics. In: Journal of Leukocyte Biology. 2014 ; Vol. 95, No. 2. pp. 285-292.
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