Function calcium-independent

Calcium-dependent regulation involves the calcium-calmodulin complex that activates smooth muscle MLCK, a monomer of approximately 135 kDa. Dephosphorylation is initiated by MLCP. MLCP is a complex of three proteins a 110-130 kDa myosin phosphatase targeting and regulatory subunit (MYPT1), a 37 kDa catalytic subunit (PP-1C) and a 20 kDa subunit of unknown function. In most cases, calcium-independent regulation of smooth muscle tone is achieved by inhibition of MLCP activity at constant calcium level inducing an increase in phospho-rMLC and contraction (Fig. 1). 

The calcium-independent ATPase of the lipid modified preparations is not only different from the calcium-dependent ATPase but also from the calcium-independent ATPase of native preparations — the basic ATPase — which has a lower nucleotide specificity126. The experiments in which the lipid matrix of the sarcoplasmic membranes has been replaced by lipid compounds not present in native membranes reveal a high degree of functional flexibility of the enzyme. On the other hand, a few residual lipids in the protein are sufficient to prevent these changes in the structure of the enzyme and to preserve its calcium sensitivity. 

Krasnoperov VG, Beavis R, Chepumy OG et al (1996) The calcium-independent receptor of a-latrotoxin is not a neurexin. Biochem Biophys Res Commun 227 868-75 Krasnoperov VG, Bittner MA, Beavis R et al (1997) a-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor. Neuron 18 925-37 Krasnoperov VG, Bittner MA, Mo W et al (2002b) Protein tyrosine phosphatase-G is a novel member of the functional family of a-latrotoxin receptors. J Biol Chem 277 35887-95 Kreienkamp HJ, Zitzer H, Gundelfinger ED et al (2000) The calcium-independent receptor for a-latrotoxin from human and rodent brains interacts with members of the ProSAP/SSTRIP/Shank family of multidomain proteins. J Biol Chem 275 32387-90 Lajus S, Lang J (2006) Splice variant 3, but not 2 of receptor protein-tyrosine phosphatase a can mediate stimulation of insulin-secretion by a-latrotoxin. J Cell Biochem 98 1552-9 Lajus S, Vacher P, Huber D et al (2006) a-Latrotoxin induces exocytosis by inhibition of voltage-dependent K+ channels and by stimulation of L-type Ca2+ channels via latrophilin in [5-cells. J Biol Chem 281 5522-31... 

Trudeau LE, Doyle RT, Emery DG et al (1996a) Calcium-independent activation of the secretory apparatus by ruthenium red in hippocampal neurons a new tool to assess modulation of presynaptic function. J Neurosci 16 46-54... 

One method is to eliminate the interference by adding an excess of another element which, combining preferentially with the interfering clement, releases the calcium. Excess added lanthanum performs this function and releases the calcium which is then atomised. The addition of lanthanum thus renders the absorbance of calcium independent of the quantity of phosphate. 

Yinstead, M.V., Balsinde, J., Dennis, E.A. 2000. Calcium-independent phospholipase A(2) structure and function. Biochim. Biophys. Acta/Mol. Cell Biol. Lipids 1488 28-39. 

Turk, 1., Ramanadham, S. 2004. The expression and function of a group VIA calcium-independent phospholipase A(2) (iPLA(2)beta) in beta-cells. Can. J. Physiol. Pharmacol. 82 824-832. 

Balsinde, J., Balboa, M.A. 200S. Cellular regulation and proposed biological functions of group VIA calcium-independent phospholipase A(2) in activated cells. Cell. Signal. 17 1052-1062. 

Akiba, S. and T. Sato. 2004. Cellular function of calcium-independent phospholipase A2. Pharm Bull 27181 1174-1178. 

As one would expect, for all its elegance, this model does not exhaust the potential functions of calcium-independent PLA2S. Evidence tallies also with a direct participation of this enzyme in arachidonate mobilization in pancreatic p cells, for example, an ATP-activated, heart-type isoform of calcium-independent PLA2 may mediate mobilization of arachidonate and subsequent formation of 12-lipoxygenase metabolites, which are thought to act as intracellular mediators in glucose-induced insulin secretion. 

Under physiologic conditions, unlike eNOS and nNOS, iNOS is not expressed constitutively in mammalian cells, but rather is induced by pro-inflammatory stimuli, such as bacterial lipopolysaccharide (LPS), or the cytokines TNF-a, ILip, or interferon-y (IFN-y), individually, or in combination. Inducible NOS possesses tightly bound calmodulin in a non-covalent manner and is calcium independent. Therefore, once expressed, iNOS continues to synthesize NO- in large amounts for a prolonged period of time. Inducible NOS activity is regulated by protein expression rather than functional modulation (Lee et al. 2003). 

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