Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins

Abstract

Ca 2 þ flux from permeabilised COS cells, we demonstrated that CaBPs decrease the sensitivity of InsP 3 -induced Ca 2 þ release (IICR). In addition, we found a Ca 2 þ -independent interaction between CaBP1 and the NH 2 -terminal 159 amino acids of the type 1 InsP 3 R. This interaction resulted in decreased InsP 3 binding to the receptor reminiscent of that observed for CaM. Unlike CaM, however, CaBPs do not inhibit ryanodine receptors, have a higher affinity for InsP 3 Rs and more potently inhibited IICR. We also show that phosphorylation of CaBP1 at a casein kinase 2 consensus site regulates its inhibition of IICR. Our data suggest that CaBPs are endogenous regulators of InsP 3 Rs tuning the sensitivity of cells to InsP 3 .

Nuclear magnetic resonance structure of calcium‐binding protein 1 in a Ca2+‐bound closed state: Implications for target recognition

“…The structure of the CaBP1 C-domain is quite similar to that of CaM, and thus, the C-domain alone (also called calbrain 19 ) exhibits Ca 2þ -dependent and tight binding to particular CaM-binding motifs in L-type Ca 2þ channels 22 and the N-terminal ligand-binding domain of InsP3Rs. 13,20 By contrast, the CaBP1 N-domain alone does not bind to these same sites. Nevertheless, the CaBP1 N-domain is essential for membrane-targeting 21 and calcium-dependent facilitation of L-type Ca 2þ channels, 22 suggesting that the N-domain serves a regulatory function.…”

IP3 Receptors: Toward Understanding Their Activation

“…There are reports of IP 3 -independent activation of IP 3 R by CaBP1 (Yang et al 2002), a member of the neuronal Ca 2þ -sensor family, and by Gbg subunits (Zeng et al 2003), but the physiological relevance is unclear (Haynes et al 2004;Nadif Kasri et al 2004). The current consensus is that binding of IP 3 to the IP 3 R is essential for its activation, but whether all four IP 3 -binding sites of the tetrameric IP 3 R must be occupied is unresolved.…”

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. This high affinity binding may result from the exposure of a distinct hydrophobic patch revealed in the carboxyl terminus of CaBP1 upon Ca 2þ -binding Li et al 2009).…”

“…CaBP1-Long and -Short have been found to have roles in the regulation of various Ca 2þ -channels including P/ Q-type (Ca V 2.1) channels (Lee et al 2002), L-type (Ca V 1.2) channels (Zhou et al 2005;Cui et al 2007), TRPC5 channels (KinoshitaKawada et al 2005, and IP 3 Rs (Yang et al 2002), which they apparently inhibit Kasri et al 2004). The interaction of Ca V 2.1 with CaBP1 appears to rely acutely upon amino-terminal myristoylation.…”