Open AccessTermination and activation of store‐operated cyclic AMP production
Author(s) -
Maiellaro Isabella,
Lefkimmiatis Konstantinos,
Moyer Mary Pat,
Curci Silvana,
Hofer Aldebaran M.
Publication year - 2012
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2012.01592.x
Subject(s) - endoplasmic reticulum , orai1 , adenylyl cyclase , stim1 , microbiology and biotechnology , crosstalk , gene isoform , gene silencing , biology , enzyme , chemistry , signal transduction , biochemistry , gene , physics , optics
Diverse pathophysiological processes (e.g. obesity, lifespan determination, addiction and male fertility) have been linked to the expression of specific isoforms of the adenylyl cyclases (AC1‐AC10), the enzymes that generate cyclic AMP ( cAMP ). Our laboratory recently discovered a new mode of cAMP production, prominent in certain cell types, that is stimulated by any manoeuvre causing reduction of free [Ca 2+ ] within the lumen of the endoplasmic reticulum (ER) calcium store. Activation of this ‘store‐operated’ pathway requires the ER Ca 2+ sensor, STIM1, but the identity of the enzymes responsible for cAMP production and how this process is regulated is unknown. Here, we used sensitive FRET‐based sensors for cAMP in single cells combined with silencing and overexpression approaches to show that store‐operated cAMP production occurred preferentially via the isoform AC3 in NCM460 colonic epithelial cells. Ca 2+ entry via the plasma membrane Ca 2+ channel, Orai1, suppressed cAMP production, independent of store refilling. These findings are an important first step towards defining the functional significance and to identify the protein composition of this novel Ca 2+ / cAMP crosstalk system.