Atypical calcium regulation of the PKD2-L1 polycystin ion channel
| Title: | Atypical calcium regulation of the PKD2-L1 polycystin ion channel |
| Author: |
DeCaen, Paul G; Liu, Xiaowen; Abiria, Sunday; Clapham, David E
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | DeCaen, Paul G, Xiaowen Liu, Sunday Abiria, and David E Clapham. 2016. “Atypical calcium regulation of the PKD2-L1 polycystin ion channel.” eLife 5 (1): e13413. doi:10.7554/eLife.13413. http://dx.doi.org/10.7554/eLife.13413. |
| Full Text & Related Files: |
4922860.pdf (6.476Mb; PDF) 
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| Abstract: | Native PKD2-L1 channel subunits are present in primary cilia and other restricted cellular spaces. Here we investigate the mechanism for the channel's unusual regulation by external calcium, and rationalize this behavior to its specialized function. We report that the human PKD2-L1 selectivity filter is partially selective to calcium ions (Ca2+) moving into the cell, but blocked by high internal Ca2+concentrations, a unique feature of this transient receptor potential (TRP) channel family member. Surprisingly, we find that the C-terminal EF-hands and coiled-coil domains do not contribute to PKD2-L1 Ca2+-induced potentiation and inactivation. We propose a model in which prolonged channel activity results in calcium accumulation, triggering outward-moving Ca2+ ions to block PKD2-L1 in a high-affinity interaction with the innermost acidic residue (D523) of the selectivity filter and subsequent long-term channel inactivation. This response rectifies Ca2+ flow, enabling Ca2+ to enter but not leave small compartments such as the cilium. DOI: http://dx.doi.org/10.7554/eLife.13413.001 |
| Published Version: | doi:10.7554/eLife.13413 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922860/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:27822289 |
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