PT  - JOURNAL ARTICLE
AU  - Gaya P Yadav
AU  - Hui Zheng
AU  - Qing Yang
AU  - Lauren G Douma
AU  - Linda B Bloom
AU  - Qiu-Xing Jiang
TI  - Secretory granule protein chromogranin B (CHGB) forms an anion channel in membranes
AID  - 10.26508/lsa.201800139
DP  - 2018 Oct 01
TA  - Life Science Alliance
PG  - e201800139
VI  - 1
IP  - 5
4099  - https://www.life-science-alliance.org/content/1/5/e201800139.short
4100  - https://www.life-science-alliance.org/content/1/5/e201800139.full
SO  - Life Sci. Alliance2018 Oct 01; 1
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.