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)

Characterization of Cav1.4 Complexes (α11.4, β2, and α2δ4) in HEK293T Cells and in the Retina

“…The absence of this facilitation, in addition to relatively weak voltage dependence of activation, in ␣ 2 ␦ 4 -containing Ca v 1.4 channels might be considered maladaptive in terms of supporting synaptic Ca 2ϩ signals that drive photoreceptor transmission. However, native Ca v 1.4 channels would also be associated with CaBP4, which significantly enhances voltage-dependent activation of Ca v 1.4 (28,42). Thus, native ␣ 2 ␦ 4 -containing Ca v 1.4 channels in photoreceptors may be more strongly modulated by CaBP4 than ␣ 2 ␦ 1 -containing Ca v 1.4 channels.…”

“…High magnification images showed anti-Ca v 1.4 ␣ 1 labeling of elongated and horseshoeshaped structures corresponding to the photoreceptor synaptic ribbon that arches around the postsynaptic terminals, as described previously (13,33). In these experiments, we also tested for the co-immunoprecipitation of CaBP4, a known Ca v 1.4-interacting protein (28,42). Because the association of CaBP4 with Ca v 1.4 can be affected by Ca 2ϩ , coimmunoprecipitation experiments were done in the presence and absence of Ca 2ϩ .…”

Competitive and Non-competitive Regulation of Calcium-dependent Inactivation in CaV1.2 L-type Ca2+ Channels by Calmodulin and Ca2+-binding Protein 1

“…CaBP1 regulates the currents of Ca V 1 and Ca V 2 channels in neurons, photoreceptors, and auditory hair cells. CaBP interactions with Ca v 1 channels may be required for hearing and vision, as mutations that disrupt these interactions cause blindness and deafness (17,18). Although CaBP1 is structurally similar to CaM, with two Ca 2ϩ binding lobes, it has a low sensitivity to Ca 2ϩ in the N-lobe and a myristoylation motif at its NT (19 -21).…”

“…Specifically, Ca 2ϩ -binding proteins regulate the inactivation, activation gating, and surface expression of VGCCs (12)(13)(14)(15)(16)(17). CaBP1 regulates the currents of Ca V 1 and Ca V 2 channels in neurons, photoreceptors, and auditory hair cells.…”

Protein Phosphatase 2A Dephosphorylates CaBP4 and Regulates CaBP4 Function

“…2013;54:1214-1226) DOI:10.1167/iovs.12-11319 C aBP4 is a member of a subfamily of calmodulin-like neuronal Ca 2þ -binding proteins (CaBP1-8). [1][2][3][4] In addition to modulating voltage-gated Ca v Ca 2þ channels, [5][6][7][8][9][10][11][12][13] CaBP family members modulate transient receptor potential (TRP) channels and inositol 1,4,5-trisphosphate (IP 3 ) receptors, [14][15][16][17] CaBP4 is localized in photoreceptor synaptic terminals and in cochlear inner hair cells. 7,10,12,18 CaBP4 is essential for photoreceptor synaptic function through enhanced activation of Ca v 1.4 L-type voltage-gated Ca 2þ channels and transmitter release.…”