A New Role for IQ Motif Proteins in Regulating Calmodulin Function

IQ-Motif Proteins Influence Intracellular Free Ca2+in Hippocampal Neurons Through Their Interactions With Calmodulin

“…1A) but it does not change the Ca 2ϩ association rate ). We assume Ng affects only the C-lobe of CaM, as supported by present experimental evidence Putkey et al 2003). Thus each CaM molecule undergoes transitions between 18 (6 ϫ 3) activation states involving association and dissociation of Ca 2ϩ and Ng (6 different states for the C-terminal lobe and 3 for N-lobe).…”

“…An interesting example is PEP-19, another IQ-motif protein that has an impact on the Ca 2ϩ -binding properties of CaM different from that of Ng. PEP-19 increases (ϳ30-to 40-fold) both the Ca 2ϩ association rate (k 9 ) and dissociation rate (k Ϫ9 ) of CaM to a similar degree (see Table 1) (Putkey et al 2003). Because PEP-19 does not change the dissociation constant (ϭk Ϫ9 /k 9 ), the steady-state level of free Ca 2ϩ will remain the same.…”

“…Ng and PEP-19 are the members of the IQ-motif protein family and these two proteins accelerate the Ca 2ϩ dissociation from the C-terminal lobe of CaM Putkey et al 2003). We hypothesized these proteins may have a significant impact on the intracellular free Ca 2ϩ by regulating the Ca 2ϩ buffering capacity of CaM.…”

“…This corresponds to about 37-100 M of CaM (assuming the protein content is 0.25 g/ml cell volume as in Huang et al 2004). CaM binds four Ca 2ϩ ions: two Ca 2ϩ ions bind in a cooperative fashion to each lobe (Babu et al 1985;Gaertner et al 2004;Putkey et al 2003). Therefore CaM equips hippocampal neurons with about 148 -400 M of Ca 2ϩ -binding sites.…”

“…Neurogranin (Ng) is such a protein and its effect on the Ca 2ϩ -binding kinetics of CaM was recently identified (Gaertner 2004;Gaertner et al 2004;Putkey et al 2003). Neurogranin (Ng) and a related protein, PEP-19, are members of the IQ-motif family of CaM-binding proteins that interact with apo-CaM and Ca 2ϩ -CaM.…”