Transient fusion ensures granule replenishment to enable repeated release after IgE-mediated mast cell degranulation

J Cell Sci. 2016 Nov 1;129(21):3989-4000. doi: 10.1242/jcs.194340. Epub 2016 Sep 13.

Abstract

To ensure normal immune function, mast cells employ different pathways to release mediators. Here, we report a thus far unknown capacity of mast cells to recycle and reuse secretory granules after an antigen-evoked degranulation process under physiological conditions; this phenomenon involves the existence of a recycling secretory granule pool that is available for release in a short time scale. Rapid endocytic modes contributed to the recycling of ∼60% of the total secretory granule population, which involved kiss-and-run and cavicapture mechanisms, causing retention of the intragranular matrix. We found the presence of normal-size granules and giant actomyosin- and dynamin-dependent granules, which were characterized by large quantal content. These large structures allowed the recovered mast cells to release a large amount of 5-HT, compensating for the decrease in the number of exocytosed secretory granules. This work uncovers a new physiological role of the exo-endocytosis cycle in the immunological plasticity of mast cells and reveals a new property of their biological secretion.

Keywords: Cavicapture; Endocytosis; Exocytosis; Kiss-and-run; Mast cell; Proteoglycan.

MeSH terms

  • Actins / metabolism
  • Animals
  • Antigens / metabolism
  • Calcimycin / pharmacology
  • Cell Degranulation* / drug effects
  • Dynamins / metabolism
  • Electrochemical Techniques
  • Endocytosis / drug effects
  • Exocytosis / drug effects
  • Immunoglobulin E / metabolism*
  • Mast Cells / drug effects
  • Mast Cells / physiology*
  • Membrane Fusion* / drug effects
  • Mice, Inbred C57BL
  • Models, Biological
  • Myosin Type II / metabolism
  • Secretory Vesicles / drug effects
  • Secretory Vesicles / metabolism*
  • Serotonin / metabolism

Substances

  • Actins
  • Antigens
  • Serotonin
  • Immunoglobulin E
  • Calcimycin
  • Myosin Type II
  • Dynamins