| First Author | Hall DD | Year | 2013 |
| Journal | Neuron | Volume | 78 |
| Issue | 3 | Pages | 483-97 |
| PubMed ID | 23664615 | Mgi Jnum | J:197980 |
| Mgi Id | MGI:5495056 | Doi | 10.1016/j.neuron.2013.02.032 |
| Citation | Hall DD, et al. (2013) Competition between alpha-actinin and Ca(2)(+)-calmodulin controls surface retention of the L-type Ca(2)(+) channel Ca(V)1.2. Neuron 78(3):483-97 |
| abstractText | Regulation of neuronal excitability and cardiac excitation-contraction coupling requires the proper localization of L-type Ca(2)(+) channels. We show that the actin-binding protein alpha-actinin binds to the C-terminal surface targeting motif of alpha11.2, the central pore-forming Ca(V)1.2 subunit, in order to foster its surface expression. Disruption of alpha-actinin function by dominant-negative or small hairpin RNA constructs reduces Ca(V)1.2 surface localization in human embryonic kidney 293 and neuronal cultures and dendritic spine localization in neurons. We demonstrate that calmodulin displaces alpha-actinin from their shared binding site on alpha11.2 upon Ca(2)(+) influx through L-type channels, but not through NMDAR, thereby triggering loss of Ca(V)1.2 from spines. Coexpression of a Ca(2)(+)-binding-deficient calmodulin mutant does not affect basal Ca(V)1.2 surface expression but inhibits its internalization upon Ca(2)(+) influx. We conclude that alpha-actinin stabilizes Ca(V)1.2 at the plasma membrane and that its displacement by Ca(2)(+)-calmodulin triggers Ca(2)(+)-induced endocytosis of Ca(V)1.2, thus providing an important negative feedback mechanism for Ca(2)(+) influx. |
