Synaptotagmin-2 controls regulated exocytosis but not other secretory responses of mast cells.
Mast cell degranulation is a highly regulated, calcium-dependent process, which is important for the acute release of inflammatory mediators during the course of many pathological conditions. We previously found that Synaptotagmin-2, a calcium sensor in neuronal exocytosis, was expressed in a mast cell line. We postulated that this protein may be involved in the control of mast cell-regulated exocytosis, and we generated Synaptotagmin-2 knock-out mice to test our hypothesis. Mast cells from this mutant animal conferred an abnormally decreased passive cutaneous anaphylaxis reaction on mast cell-deficient mice that correlated with a specific defect in mast cell-regulated exocytosis, leaving constitutive exocytosis and nonexocytic mast cell effector responses intact. This defect was not secondary to abnormalities in the development, maturation, migration, morphology, synthesis, and storage of inflammatory mediators, or intracellular calcium transients of the mast cells. Unlike neurons, the lack of Synaptotagmin-2 in mast cells was not associated with increased spontaneous exocytosis.
Melicoff
Ernestina
E
Department of Pulmonary Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Sansores-Garcia
Leticia
L
Gomez
Alejandra
A
Moreira
Daniel C
DC
Datta
Proleta
P
Thakur
Pratima
P
Petrova
Youlia
Y
Siddiqi
Tanya
T
Murthy
Jayasimha N
JN
Dickey
Burton F
BF
Heidelberger
Ruth
R
Adachi
Roberto
R
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D005089:Exocytosis; D005260:Female; D006967:Hypersensitivity / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008407:Mast Cells / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D050861:Synaptotagmin II / Q000235:genetics / Q000378:metabolism*
D050861:Synaptotagmin II; C494263:Syt2 protein, mouse; D002118:Calcium