Ca2+/Calmodulin Regulates Trafficking of CaV1.2 Ca2+Channels in Cultured Hippocampal Neurons

Wang, Honggang; George, Mark S.; Kim, James; Wang, Chaojian; Pitt, Geoffrey S.

doi:10.1523/jneurosci.1720-07.2007

Cited by 56 publications

(60 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, Ca V ␤-induced membrane expression was unaffected by the complete deletion of the high affinity Ca 2ϩ /CaM IQ-binding site (⌬C1643-1666), suggesting that high affinity Ca 2ϩ /CaM binding to this domain (1643-1666) is not required. In contrast, deletion of the larger 1623-1666 region in the C terminus and mutation of the TLF site, located in a pre-IQ apocalmodulin-binding site, abolished plasma membrane targeting of Ca V 1.2 in agreement with previous reports (43,44,50). Clearly the C terminus of Ca V 1.2 harbors key site targeting signals, but our current data do not support a model whereby high affinity Ca 2ϩ /CaM binding to the IQ domain (1643-1666) is required.…”

Section: Discussionsupporting

confidence: 92%

Molecular Determinants of the CaVβ-induced Plasma Membrane Targeting of the CaV1.2 Channel

Bourdin

Marger

Wall-Lacelle

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Voltage-dependent Ca 2ϩ channels (Ca V ) are membrane proteins that play a key role in promoting Ca 2ϩ influx in response to membrane depolarization in excitable cells. To this date, molecular cloning has identified the primary structures for 10 distinct calcium channel Ca V ␣ 1 subunits (1-7) that are classified into three main subfamilies according to their high voltageactivated (HVA) 2 gating (Ca V 1 and Ca V 2) or low voltage-activated gating (Ca V 3). In addition to the transmembrane poreforming Ca V ␣1 subunit, Ca V 1 and Ca V 2 channels arise from the multimerization of three other proteins (7): a cytoplasmic Ca V ␤ subunit, a mostly extracellular Ca V ␣2␦ subunit, and calmodulin constitutively bound to the C terminus of Ca V ␣1 (8 -12).A considerable body of work documents the interaction and modulation of the Ca V ␣1 subunit of Ca V 1 and Ca V 2 channels (13-18) by the auxiliary Ca V ␤. The high affinity Ca V ␣1-Ca V ␤ interaction site on the pore-forming Ca V ␣1 subunit is a conserved 18-residue sequence in the I-II linker called the ␣ interaction domain (AID) (19,20) that has been structurally resolved by high resolution x-ray crystallography (21-23). Structural work showed that the AID forms a ␣-helix that binds to the ␣ binding pocket (ABP) in the Ca V ␤ nucleotide kinase (NK) domain. It has been proposed that the MMQKAL cluster of residues within the latter determines the high affinity nanomolar interaction between the two proteins (24 -29). Numerous mutational analyses of the AID residues have correlated the Ca V ␤-induced biophysical modulation with the high affinity binding of Ca V ␤ to the AID peptide in a variety of Ca V ␣1 isoforms for Ca V 1 and Ca V 2 channels (25, 29 -32).The association of Ca V ␣1 and Ca V ␤ subunits is also critical for proper channel maturation and cell surface expression of Ca V 2.2 (17), Ca V 1.2 (33, 34), and Ca V 2.3 (35). In Ca V 2.2, the I-II linker is presumed to play a role in this process (17,18), and mutations within the AID motif eliminated its cell surface expression and biophysical modulation by Ca V ␤1b and Ca V ␤3 (32). In addition, the Ca V ␤2-induced increase in Ca V 1.2 whole cell currents was abolished with the AID-defective YWI/AAA mutant (29), suggesting that high affinity binding of Ca V ␤ onto AID is required to traffic Ca V ␣1 to the plasma membrane. Nonetheless, the unique character of the high affinity AID-ABP interface in the membrane targeting of Ca V ␣1 has been questioned (27, 36 -40). In particular, it has been suggested that Ca V ␤-mediated plasma membrane targeting could be uncoupled from Ca V ␤-mediated modulation of channel gating (26, 41) with important contributions from other intracellular regions (33, 39,(42)(43)(44).In addition to Ca V ␤, the ancillary subunit Ca V ␣2␦ and the ubiquitous calmodulin (CaM) protein have also been proposed to modulate HVA channel maturation and targeting (9). For instance, co-expression of Ca V ␣2␦ promoted the trafficking of the Ca V ␣1 subunit of Ca V 2.2 in COS-7 cells (45), suggesting that Ca V ␣2...

show abstract

Section: Discussionsupporting

confidence: 92%

Molecular Determinants of the CaVβ-induced Plasma Membrane Targeting of the CaV1.2 Channel

Bourdin

Marger

Wall-Lacelle

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…2C). Importantly, similar to prior reports with untagged subunits, 26 in the presence 500 μM Ca 2+ the CaM-mCherry-Ca v 1.2 interaction was readily observed and directly demonstrated that overexpressed CaM binds the channel (Fig. 2C).…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tsupporting

confidence: 88%

Calmodulin overexpression does not alter Ca_v1.2 function or oligomerization state

et al. 2011

View full text Add to dashboard Cite

“…Although we cannot completely exclude a CaM-independent mechanism, it is very likely that CaM binding to the IQ domain masks an endoplasmic reticulum retention signal within this domain as proposed for Cav1.2 (43). In Cav1.2, such a mechanism regulates trafficking to distal dendrites in hippocampal neurons (44). Furthermore, our data clearly indicate that CaM plays a role in the regulation of VDI in Cav1.…”

Section: Discussionmentioning

confidence: 57%

Calmodulin Is a Functional Regulator of Cav1.4 L-type Ca2+ Channels

Griessmeier

Cuny

Rötzer

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

Our data indicate that calmodulin is preassociated with the C terminus of Cav1.4 but may be tethered in a different steric orientation as compared with other Ca 2؉ channels. We also find that calmodulin is important for Cav1.4 function because it increases current density and slows down voltagedependent inactivation. Our data show that the ICDI domain selectively abolishes Ca 2؉ -dependent inactivation, whereas it does not interfere with other calmodulin effects.

show abstract

Ca²⁺/Calmodulin Regulates Trafficking of Ca_V1.2 Ca²⁺Channels in Cultured Hippocampal Neurons

Cited by 56 publications

References 38 publications

Molecular Determinants of the CaVβ-induced Plasma Membrane Targeting of the CaV1.2 Channel

Molecular Determinants of the CaVβ-induced Plasma Membrane Targeting of the CaV1.2 Channel

Calmodulin overexpression does not alter Ca_v1.2 function or oligomerization state

Calmodulin Is a Functional Regulator of Cav1.4 L-type Ca2+ Channels

Contact Info

Product

Resources

About

Ca2+/Calmodulin Regulates Trafficking of CaV1.2 Ca2+Channels in Cultured Hippocampal Neurons

Cited by 56 publications

References 38 publications

Molecular Determinants of the CaVβ-induced Plasma Membrane Targeting of the CaV1.2 Channel

Molecular Determinants of the CaVβ-induced Plasma Membrane Targeting of the CaV1.2 Channel

Calmodulin overexpression does not alter Cav1.2 function or oligomerization state

Calmodulin Is a Functional Regulator of Cav1.4 L-type Ca2+ Channels

Contact Info

Product

Resources

About

Ca²⁺/Calmodulin Regulates Trafficking of Ca_V1.2 Ca²⁺Channels in Cultured Hippocampal Neurons

Calmodulin overexpression does not alter Ca_v1.2 function or oligomerization state