Unknown

Dataset Information

0

Competition between ?-actinin and Ca²?-calmodulin controls surface retention of the L-type Ca²? channel Ca(V)1.2.


ABSTRACT: Regulation of neuronal excitability and cardiac excitation-contraction coupling requires the proper localization of L-type Ca²? channels. We show that the actin-binding protein ?-actinin binds to the C-terminal surface targeting motif of ?11.2, the central pore-forming Ca(V)1.2 subunit, in order to foster its surface expression. Disruption of ?-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 ?-actinin from their shared binding site on ?11.2 upon Ca²? influx through L-type channels, but not through NMDAR, thereby triggering loss of Ca(V)1.2 from spines. Coexpression of a Ca²?-binding-deficient calmodulin mutant does not affect basal Ca(V)1.2 surface expression but inhibits its internalization upon Ca²? influx. We conclude that ?-actinin stabilizes Ca(V)1.2 at the plasma membrane and that its displacement by Ca²?-calmodulin triggers Ca²?-induced endocytosis of Ca(V)1.2, thus providing an important negative feedback mechanism for Ca²? influx.

SUBMITTER: Hall DD 

PROVIDER: S-EPMC4570828 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

altmetric image

Publications


Regulation of neuronal excitability and cardiac excitation-contraction coupling requires the proper localization of L-type Ca²⁺ channels. We show that the actin-binding protein α-actinin binds to the C-terminal surface targeting motif of α11.2, the central pore-forming Ca(V)1.2 subunit, in order to foster its surface expression. Disruption of α-actinin function by dominant-negative or small hairpin RNA constructs reduces Ca(V)1.2 surface localization in human embryonic kidney 293 and neuronal cu  ...[more]

Similar Datasets

| S-EPMC7049811 | biostudies-literature
| S-EPMC6407617 | biostudies-literature
| S-EPMC2890469 | biostudies-literature
| S-EPMC3391132 | biostudies-literature
| S-EPMC7575592 | biostudies-literature
| S-EPMC6815189 | biostudies-literature
| S-EPMC2430375 | biostudies-literature
| S-EPMC1750862 | biostudies-literature
| S-EPMC5531164 | biostudies-literature
| S-EPMC6615562 | biostudies-literature