Synaptotagmin 2 couples mucin granule exocytosis to Ca2+ signaling from endoplasmic reticulum.
Synaptotagmin 2 (Syt2) functions as a low affinity, fast exocytic Ca(2+) sensor in neurons, where it is activated by Ca(2+) influx through voltage-gated channels. Targeted insertion of lacZ into the mouse syt2 locus reveals expression in mucin-secreting goblet cells of the airways. In these cells, rapid Ca(2+) entry from the extracellular medium does not contribute significantly to stimulated secretion (Davis, C. W., and Dickey, B. F. (2008) Annu. Rev. Physiol. 70, 487-512). Nonetheless, Syt2(-/-) mice show a severe defect in acute agonist-stimulated airway mucin secretion, and Syt2(+/-) mice show a partial defect. In contrast to Munc13-2(-/-) mice (Zhu, Y., Ehre, C., Abdullah, L. H., Sheehan, J. K., Roy, M., Evans, C. M., Dickey, B. F., and Davis, C. W. (2008) J. Physiol. (Lond.) 586, 1977-1992), Syt2(-/-) mice show no spontaneous mucin accumulation, consistent with the inhibitory action of Syt2 at resting cytoplasmic Ca(2+) in neurons. In human airway goblet cells, inositol trisphosphate receptors are found in rough endoplasmic reticulum that closely invests apical mucin granules, consistent with the known dependence of exocytic Ca(2+) signaling on intracellular stores in these cells. Hence, Syt2 can serve as an exocytic sensor for diverse Ca(2+) signaling systems, and its levels are limiting for stimulated secretory function in airway goblet cells.
Tuvim
Michael J
MJ
Department of Pulmonary Medicine, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Mospan
Andrea Rossi
AR
Burns
Kimberlie A
KA
Chua
Michael
M
Mohler
Peter J
PJ
Melicoff
Ernestina
E
Adachi
Roberto
R
Ammar-Aouchiche
Zoulikha
Z
Davis
C William
CW
Dickey
Burton F
BF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005089:Exocytosis; D005786:Gene Expression Regulation; D020397:Goblet Cells / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009077:Mucins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D050861:Synaptotagmin II / Q000378:metabolism / Q000502:physiology*
D053496:Inositol 1,4,5-Trisphosphate Receptors; D009077:Mucins; D050861:Synaptotagmin II; D002118:Calcium