Dataset Information

?-Actinin-1 promotes activity of the L-type Ca²⁺ channel Ca_v 1.2.

ABSTRACT: The L-type Ca²⁺ channel Ca_V 1.2 governs gene expression, cardiac contraction, and neuronal activity. Binding of ?-actinin to the IQ motif of Ca_V 1.2 supports its surface localization and postsynaptic targeting in neurons. We report a bi-functional mechanism that restricts Ca_V 1.2 activity to its target sites. We solved separate NMR structures of the IQ motif (residues 1,646-1,664) bound to ?-actinin-1 and to apo-calmodulin (apoCaM). The Ca_V 1.2 K1647A and Y1649A mutations, which impair ?-actinin-1 but not apoCaM binding, but not the F1658A and K1662E mutations, which impair apoCaM but not ?-actinin-1 binding, decreased single-channel open probability, gating charge movement, and its coupling to channel opening. Thus, ?-actinin recruits Ca_V 1.2 to defined surface regions and simultaneously boosts its open probability so that Ca_V 1.2 is mostly active when appropriately localized.

SUBMITTER: Turner M

PROVIDER: S-EPMC7049811 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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α-Actinin-1 promotes activity of the L-type Ca2+ channel Cav 1.2.

Turner Matthew M Anderson David E DE Bartels Peter P Nieves-Cintron Madeline M Coleman Andrea M AM Henderson Peter B PB Man Kwun Nok Mimi KNM Tseng Pang-Yen PY Yarov-Yarovoy Vladimir V Bers Donald M DM Navedo Manuel F MF Horne Mary C MC Ames James B JB Hell Johannes W JW

The EMBO journal 20200127 5

The L-type Ca2+ channel CaV 1.2 governs gene expression, cardiac contraction, and neuronal activity. Binding of α-actinin to the IQ motif of CaV 1.2 supports its surface localization and postsynaptic targeting in neurons. We report a bi-functional mechanism that restricts CaV 1.2 activity to its target sites. We solved separate NMR structures of the IQ motif (residues 1,646-1,664) bound to α-actinin-1 and to apo-calmodulin (apoCaM). The CaV ...[more]

PMID: 31985069

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Dataset Information

?-Actinin-1 promotes activity of the L-type Ca²⁺ channel Ca_v 1.2.

Publications

α-Actinin-1 promotes activity of the L-type Ca<sup>2+</sup> channel Ca<sub>v</sub> 1.2.

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Dataset Information

?-Actinin-1 promotes activity of the L-type Ca2+ channel Cav 1.2.

Publications

α-Actinin-1 promotes activity of the L-type Ca<sup>2+</sup> channel Ca<sub>v</sub> 1.2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

?-Actinin-1 promotes activity of the L-type Ca²⁺ channel Ca_v 1.2.