Ca²⁺-Binding Protein-1 Facilitates and Forms a Postsynaptic Complex with Ca_v1.2 (L-Type) Ca²⁺Channels

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

“…An essential role for CaM interaction with ␣ 1C (Ca V 1.2) in CREB-dependent gene expression was suggested by the disruption of excitation-transcription coupling when the CaM binding IQ motif in ␣ 1C was mutated (Dolmetsch et al, 2001). Because CaM is but one CaBP that has been postulated to modulate Ca 2ϩ channel function in neurons (Lee et al, 2002;Zhou et al, 2004;Lautermilch et al, 2005;Yang et al, 2006), our demonstration that CaM coimmunoprecipitates with ␣ 1C from brain lysates provides the first evidence that CaM is a bona fide Ca V 1.2 subunit and the likely Ca 2ϩ sensor for CDI and gene expression. Moreover, the recent demonstration that CaBP4 competes with CaM to modulate Ca V 1.3 channels in certain neuronal subpopulations (Yang et al, 2006) may explain the apparent differences in coupling of CREB activation to Ca V 1.2 versus Ca V 1.3 channels (Zhang et al, 2006).…”

Complex Regulation of Voltage-dependent Activation and Inactivation Properties of Retinal Voltage-gated Cav1.4 L-type Ca2+ Channels by Ca2+-binding Protein 4 (CaBP4)

“…One important possibility would be that CaBP4 binds to the IQ motif in the C-terminal tail of Cav1.4. Binding of other CaBPs and of CaM to the IQ motif of high voltage-activated and low voltage-activated Ca 2ϩ channels including Cav1.4 has been reported (6,27,(35)(36)(37). To test this possibility in our experimental setting, we performed FRET experiments using a mutant of the C terminus of Cav1.4, in which five amino acid residues within the IQ motif are replaced by alanines (1.4/5A).…”

The Diversity of Calcium Sensor Proteins in the Regulation of Neuronal Function

“…For instance, both CaBP1 and calmodulin bind to L-type Ca 2þ channels with calmodulin causing Ca 2þ -induced channel closure but CaBP1 promoting channel opening (Zhou et al 2004a;Zhou et al 2005). Both calmodulin and CaBP1 also regulate inositol 1,4,5-trisphosphate receptors (IP 3 Rs) (Yang et al 2002;Haynes et al 2004;Kasri et al 2004) with CaBP1 binding the type I IP 3 R with 100-fold higher affinity than calmodulin.…”