Calmodulin modulation

Trudeau, M. C. and Zagotta, W. N. Calcium/calmodulin modulation of olfactory and rod cyclic nucleotide-gated ion channels. /. Biol. Chem. 278 18705-18708, 2003. 

Glutamate-mediated Ca2+ entry through NMDA at the plasma membrane level and mobilization of Ca2+from intracellular stores through PLC-mediated generation of PtdIns-3/J is indispensable for the basal NF-kB activity. Three cytosolic Ca2+ sensors, calmodulin, protein kinases C (PKC), and the p2 l(ras)/phosphatidylinositol 3-kinase (Ptdlns-3K)/Akt pathways, are simultaneously involved in the steps linking the Ca2+ to NF-kB activity (Lilienbaum and Israel, 2003 Marchetti et al., 2004 Lubin et al., 2005). Calmodulin modulates calcineurin, a Ca2+-dependent protein phosphatase, which plays a role in the basal NF-kB activity, whilst stimulation of both the calmodulin kinase II and Akt kinase pathways results in the up-regulation of the transcriptional potential of the p65 subunit of NF-/cB (Lilienbaum and Israel,... 

Figure 2 Basic modular structure of all mammalian NOS isoforms. The calmodulin module is needed for electron transfer from the reductase to the heme domain and its adherence is regulated by the cytosolic Ca + concentration. The enzyme is active oniy in dimeric form.

Egea J, Espinet C, Cornelia JX. Calmodulin modulates mitogen-activated protein kinase activation in response to membrane depolarization in PC 12 cells. J Neurochem 1998 70 2554-2564. 

Calmodulin is present in leaf tissues (Watterson et al. 1980 Muto, 1982 Jarrett et al. 1982) mainly in the cytosol (90%) and to a lesser extent in mitochondria (5-9%), chloroplasts (1-2%) and the microsomal fraction ( 1%). In plant tissues, calmodulin modulates the activity of... 

Similar to nNOS, Ca2+-activated calmodulin is important for the regulation of eNOS activity. However, several other proteins interact with eNOS and regulate its activity. Heat shock protein 90 (hsp90) is found associated with eNOS and probably acts as an allosteric modulator that activates the enzyme. Caveolin-1 binds eNOS and directs it to caveolae. Caveolin-1 is viewed as an inhibitor of eNOS activity, which is being replaced by CaM upon activation of endothelial cells [2]. 

Although in in vivo circumstances an intracellular free calcium increase apparently acts as the primary modulator of contraction, it can be bypassed in highly permeabilized smooth muscle preparations where the active subunit of MLCK can be introduced to phosphorylate myosin and induce contraction. The MLCK catalyzed phosphorylation of serine-19 is seen as the necessary event in the activation of smooth muscle myosin to form crossbridges. Thus, the rising phase of force during an isometric smooth muscle contraction follows an increase in the degree of phosphorylation of myosin, and that in turn follows the transient rise of (a) cytosolic free Ca, (b) Ca-calmodulin complexes, and (c) the active form of MLCK. The regulation of the intracellular calcium is discussed below. The dynam-... 

Finally, entry of Ca + through somatic and dendritic Ca + channels activates calmodulin-dependent protein kinases to modulate transcription, and thereby plays a crucial role in certain components of neural development and plasticity. 

Churn, S. B., Rana, A., Lee, K. el al. (2002). Calcium/calmodulin-dependent kinase II phosphorylation of the GABAa receptor alphal subunit modulates benzodiazepine binding. J. Neurochem. 82, 1065-76. 

Bagni, C., Mannucci, L., Dotti, C. G., and Amaldi, F. (2000). Chemical stimulation of synaptosomes modulates alpha —Ca2+/calmodulin-dependent protein kinase II mRNA association to polysomes. J. Neurosci. 20, RC76. 

Soderling, T. R. Modulation of glutamate receptors by cal-cium/calmodulin-dependent protein kinase II. Neurochem. Int. 28 359-361,1996. 

FIGURE 50-5 A model for the transduction of odors in OSNs. The individual steps are detailed in the text. Note that several feedback loops modulate the odor response, including inhibition of the CNG channel by Ca2+ ions (purple balls) that permeate the channel, and a Ca2+/calmodulin (CaM) -mediated desensitization of the channel that underlies rapid odor adaptation. Several other mechanisms, including phosphodiesterase-mediated hydrolysis of the second messenger, cAMP, and phosphorylation of the OR by various kinases, have also been described. 

Chen, T. Y. and Yau, K. W. Direct modulation by Ca2+-calmodulin of cyclic nucleotide-activated channel of rat olfactory receptor neurons. Nature 368 545-548,1994. 

Calmodulin (CaM) undergoes drastic conformational change when it binds Ca2+ and amphiphilic peptides such as mas to po ran and endorphin, which results in the modulation of many important biochemical reactions. The N-terminal and C-terminal of rigid structured globular domains are bridged with a long flexible peptide of a-helical structure. Each domain binds two Ca2+ ions to its hydrophobic sites. 

Maulet, Y Cox, J.A. Structural changes in melittin and calmodulin upon complex formation and their modulation by calcium. Biochemistry 1983, 22, 5680-5686. 

Calcium effects. The biochemical effects of Ca "" in the cytoplasm are mediated by special Ca -binding proteins calcium sensors"). These include the annexins, calmodulin, and troponin C in muscle (see p. 334). Calmodulin is a relatively small protein (17 kDa) that occurs in all animal cells. Binding of four Ca "" ions (light blue) converts it into a regulatory element. Via a dramatic conformational change (cf 2a and 2b), Ca -calmodulin enters into interaction with other proteins and modulates their properties. Using this mechanism, Ca "" ions regulate the activity of enzymes, ion pumps, and components of the cytoskeleton. 

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