Calcium/calmodulin-dependent protein kinases function

Currie, S., Loughrey, C. M., Craig, M. A., and Smith, G. L. (2004). Calcium/Calmodulin-Dependent Protein Kinase Ildelta Associates with the Ryanodine Receptor Complex and Regulates Channel Function in Rabbit Heart. Biochem J 377(Pt 2) 357-66. 

Calcium/calmodulin-dependent protein kinase II (CaM kinase II) is a mediator of synaptic and cytoskeletal function as well as neurotransmitter release. The reduced CaM kinase II activity observed following normothermic ischemia is not seen under conditions of intraischemic hypothermia (57,110). Ubiquitin, a small protein involved in the catabolism of other abnormal proteins, is decreased following ischemia this may lead to an accumulation of abnormal proteins that affect cell function. Intraischemic hypothermia induces a significant restitution of ubiquitin compared to the normothermic condition (111). 

Braim AP, Schulman H. The multifunctional calcium/calmodulin-dependent protein kinase from form to function. Annu. Rev. Physiol. 1995 57 417 45. 

Braun, A.P. Schulman, H. (1995) Anrm. Rev. Physiol. 57, 417-445. The multifunctional calcium/ calmodulin-dependent protein kinase Ifom form to function. 

The synthesis of 5-HT can increase markedly under conditions requiring more neurotransmitter. Plasticity is an important concept in neurobiology. In general, this refers to the ability of neuronal systems to conform to either short- or long-term demands placed upon their activity or function (see Plasticity in Ch. 53). One of the processes contributing to neuronal plasticity is the ability to increase the rate of neurotransmitter synthesis and release in response to increased neuronal activity. Serotonergic neurons have this capability the synthesis of 5-HT from tryptophan is increased in a frequency-dependent manner in response to electrical stimulation of serotonergic soma [7]. The increase in synthesis results from the enhanced conversion of tryptophan to 5-HTP and is dependent on extracellular calcium ion. It is likely that the increased 5-HT synthesis results in part from alterations in the kinetic properties of tryptophan hydroxylase, perhaps due to calcium-dependent phosphorylation of the enzyme by calmodulin-dependent protein kinase II or cAMP-dependent protein kinase (PKA see Ch. 23). 

Describe the structure of calmodulin and its biochemical function. Relate calmodulin to the calmodulin-dependent protein kinase (CaM Kinase) and the Ca -ATP ion pump. Note the value of calcium ionophores, calcium buffers, and fluorescent indicators in studying the functions of Ca " in cells. 

A few enzymes, such as the previously mentioned CNP, are believed to be fairly specific for myelin/oligodendro-cytes. There is much more in the CNS than in peripheral nerve, suggesting some function more specialized to the CNS. In addition, a unique pH 7.2 cholesterol ester hydrolase is also enriched in myelin. On the other hand, there are many enzymes that are not myelin-specific but appear to be intrinsic to myelin and not contaminants. These include cAMP-stimulated kinase, calcium/calmodulin-dependent kinase, protein kinase C, a neutral protease activity and phosphoprotein phosphatases. The protein kinase C and phosphatase activities are presumed to be responsible for the rapid turnover of MBP phosphate groups, and the PLP acylation enzyme activity is also intrinsic to myelin. 

Ryanodine receptors are a family of intracellular Ca release channels that were originally identified in the sarcoplasmic reticulum of skeletal muscle cells. Three members of the family were distinguished, RyR2 ryanodine receptors in the cardiac muscle. RyRl (in the skeletal muscle) and RyR2 function as Ca release chaimels from the sarcoplasmic reticulum intracellular calcium store and play a crucial role in the exdtation-contraction cycle. They bind and calmodulin and become phosphorylated by various protein kinases including Ca /calmodulin- and cAMP-dependent kinases (Lokuta etal. 1995, Mayrleitner etal. 1995). 

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