Influx-Operated Ca(2+) Entry via PKD2-L1 and PKD1-L3 Channels Facilitates Sensory Responses to Polymodal Transient Stimuli.
The polycystic TRP subfamily member PKD2-L1, in complex with PKD1-L3, is involved in physiological responses to diverse stimuli. A major challenge to understanding whether and how PKD2-L1/PKD1-L3 acts as a bona fide molecular transducer is that recombinant channels usually respond with small or undetectable currents. Here, we discover a type of Ca(2+) influx-operated Ca(2+) entry (ICE) that generates pronounced Ca(2+) spikes. Triggered by rapid onset/offset of Ca(2+), voltage, or acid stimuli, Ca(2+)-dependent activation amplifies a small Ca(2+) influx via the channel. Ca(2+) concurrently drives a self-limiting negative feedback (Ca(2+)-dependent inactivation) that is regulated by the Ca(2+)-binding EF hands of PKD2-L1. Our results suggest a biphasic ICE with opposite Ca(2+) feedback regulation that facilitates sensory responses to multimodal transient stimuli. We suggest that such a mechanism may also occur for other sensory modalities and other Ca(2+) channels.
X-Lab for Transmembrane Signaling Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
Mingfeng
M
Hu
X-Lab for Transmembrane Signaling Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
Yuxia
Y
Liu
X-Lab for Transmembrane Signaling Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
Jinzhi
J
Wu
X-Lab for Transmembrane Signaling Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China; IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing 100084, China. Electronic address: liuxiaodong@tsinghua.edu.cn.
Xiaodong
X
Liu
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D003412:Cricetulus; D004594:Electrophysiology; D006801:Humans; D051379:Mice; D011956:Receptors, Cell Surface / Q000378:metabolism*; D050396:TRPP Cation Channels / Q000378:metabolism*
D015220:Calcium Channels; C512453:PKD1L3 protein, mouse; C486487:Pkd2l1 protein, mouse; D011956:Receptors, Cell Surface; D050396:TRPP Cation Channels; D002118:Calcium