RT Journal Article SR Electronic T1 Secretory granule protein chromogranin B (CHGB) forms an anion channel in membranes JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800139 DO 10.26508/lsa.201800139 VO 1 IS 5 A1 Gaya P Yadav A1 Hui Zheng A1 Qing Yang A1 Lauren G Douma A1 Linda B Bloom A1 Qiu-Xing Jiang YR 2018 UL https://www.life-science-alliance.org/content/1/5/e201800139.abstract AB Regulated secretion is an intracellular pathway that is highly conserved from protists to humans. Granin family proteins were proposed to participate in the biogenesis, maturation and release of secretory granules in this pathway. However, the exact molecular mechanisms underlying the intracellular functions of the granin family proteins remain unclear. Here, we show that chromogranin B (CHGB), a secretory granule protein, inserts itself into membrane and forms a chloride-conducting channel. CHGB interacts strongly with phospholipid membranes through two amphipathic α helices. At a high local concentration, CHGB insertion in membrane causes significant bilayer remodeling, producing protein-coated nanoparticles and nanotubules. Fast kinetics and high cooperativity for anion efflux from CHGB vesicles suggest that CHGB tetramerizes to form a functional channel with a single-channel conductance of ∼125 pS (150/150 mM Cl−). The CHGB channel is sensitive to an anion channel blocker and exhibits higher anion selectivity than the other six known families of Cl− channels. Our data suggest that the CHGB subfamily of granin proteins forms a new family of organelle chloride channels.