| Autor: |
Kadurin, I., Ferron, L., Rothwell, S.W., Meyer, J.O., Douglas, L.R., Bauer, C.S., Lana, B., Margas, W., Alexopoulos, O., Nieto-Rostro, M., Pratt, W.S., Dolphin, A.C. |
| Jazyk: |
angličtina |
| Rok vydání: |
2016 |
| Zdroj: |
eLife |
| Popis: |
The auxiliary α2δ subunits of voltage-gated calcium channels are extracellular membrane-associated proteins, which are post-translationally cleaved into disulfide-linked polypeptides α2 and δ. We now show, using α2δ constructs containing artificial cleavage sites, that this processing is an essential step permitting voltage-dependent activation of plasma membrane N-type (CaV2.2) calcium channels. Indeed, uncleaved α2δ inhibits native calcium currents in mammalian neurons. By inducing acute cell-surface proteolytic cleavage of α2δ, voltage-dependent activation of channels is promoted, independent from the trafficking role of α2δ. Uncleaved α2δ does not support trafficking of CaV2.2 channel complexes into neuronal processes, and inhibits Ca2+ entry into synaptic boutons, and we can reverse this by controlled intracellular proteolytic cleavage. We propose a model whereby uncleaved α2δ subunits maintain immature calcium channels in an inhibited state. Proteolytic processing of α2δ then permits voltage-dependent activation of the channels, acting as a checkpoint allowing trafficking only of mature calcium channel complexes into neuronal processes. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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