High impact information on calmodulin

• Calcium/calmodulin-dependent serine/threonine kinase type II (CaMKII) is one of the most abundant proteins in the mammalian brain, where it is thought to regulate synaptic plasticity and other processes [1].
• The functionally mapped catalytic domain of MHCK A shows no detectable sequence similarity to known classes of eukaryotic protein kinases but shares substantial sequence similarity with a transcribed Caenorhabditis elegans gene and with the mammalian elongation factor-2 kinase (calcium/calmodulin-dependent protein kinase III) [2].
• Regulation of CaMKII kinase activity occurs through an autoinhibitory mechanism in which a regulatory domain of the kinase occupies the catalytic site and calcium/calmodulin activates the kinase by binding to and displacing this regulatory domain [3].
• Our results suggest that the activation of UNC-43 by calcium/calmodulin displaces the autoinhibitory domain, thereby exposing key residues of the catalytic domain that allow for protein translocation to the neurites [3].
• Deletion of an amphiphilic basic amino-acid sequence (residues 243-256) predicted to form an alpha-helix located in the proximal region of its pleckstrin homology (PH) domain demonstrates the location of the CaM-binding domain [4].

Biological context of calmodulin

• Treatment with the calmodulin inhibitors, trifluoperazine, chlorpromazine, or W7, also induces spermiogenesis in vitro with a half maximal effect at 20 microM [5].
• Both the CO II and calmodulin genes show extreme conservation of amino acid sequences [6].
• Mode and tempo of molecular evolution in the nematode caenorhabditis: cytochrome oxidase II and calmodulin sequences [6].
• Through direct sequencing methods, the mitochondrial gene for cytochrome oxidase subunit two (CO II) and the single-copy nuclear gene for calmodulin were compared among strains of Caenorhabidits elegans and two other Caenorhabditis species (C. remanei and C. briggsae) [6].
• Functional analysis of the single calmodulin gene in the nematode Caenorhabditis elegans by RNA interference and 4-D microscopy [7].

Associations of calmodulin with chemical compounds

• Other genes induced across most timepoints included lipoxygenase, calmodulin, phospholipase C, metallothionein-like protein, and chalcone reductase [8].
• The C domain of netrin UNC-6 silences calcium/calmodulin-dependent protein kinase- and diacylglycerol-dependent axon branching in Caenorhabditis elegans [9].
• Grb7Delta maintains in part the capacity to bind phosphoinositides, and CaM competes for phosphoinositide binding [4].
• The cell-permeable CaM antagonist W7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide), but not the CaM-dependent protein kinase II inhibitor KN93, prevents this effect [4].
• Calmodulin (CaM) is a ubiquitous calcium (Ca(2+)) sensor which binds and regulates protein serine/threonine kinases along with many other proteins in a Ca(2+)-dependent manner [10].

Other interactions of calmodulin

• The signaling cascade is only partially dependent on the phospholipase C beta (EGL-8) and is negatively regulated by G alpha(o) [GOA-1 (G-protein, O, alpha subunit family member 1)] and calcium/calmodulin-dependent kinase [UNC-43 (uncoordinated family member 43)] [11].
• The polypeptide predicted from the sequence of this gene displays structural features of both calmodulin and troponin C [12].
• The cDNA sequence of this gene, which has been designated Obscurin-myosin light chain kinase (Obscurin-MLCK), would be predicted to encode for at least 68 immunoglobulin domains, two fibronectin domains, one calcium/calmodulin binding domain, a RhoGTP exchange factor domain, and two serine-threonine kinase domains [13].

Analytical, diagnostic and therapeutic context of calmodulin

• Finally, we show that RNAi delivery by the feeding protocol does not allow the efficient silencing of the CaM gene obtained by microinjection [7].

References