Regulation of epithelial ion transport in exocrine glands by store-operated Ca 2+ entry

Store-operated Ca entry (SOCE) is a conserved mechanism of Ca influx that regulates Ca signaling in many cell types. SOCE is activated by depletion of endoplasmic reticulum (ER) Ca stores in response to physiological agonist stimulation. After it was first postulated by J.W. Putney Jr. in 1986, SOCE has been described in a large number of non-excitable cell types including secretory cells of different exocrine glands. Here we discuss the mechanisms by which SOCE controls salt and fluid secretion in exocrine glands, with a special focus on eccrine sweat glands. In sweat glands, SOCE plays an important, non-redundant role in regulating the function of Ca -activated Cl channels (CaCC), Cl secretion and sweat production. In the absence of key regulators of SOCE such as the CRAC channel pore subunit ORAI1 and its activator STIM1, the Ca -activated chloride channel TMEM16A is inactive and fails to secrete Cl , resulting in anhidrosis in mice and human patients.