Calmodulin role

Van Lierop, J.E. Wilson, D.P. Davis, J.P. Tikunova, S. Sutherland, C. Walsh, M.P. Johnson, J.D. Activation of smooth muscle myosin light chain kinase by calmodulin. Role of Lys30 and Gly40. J. Biol. Chem., 277, 6550-6558 (2002)... 

Small ubiquitous calcium-binding protein. Calmodulin binds and regulates the activity of many protein targets involved in cellular signal transduction pathways mediated by calcium. Calmodulin is ranked among the most conserved proteins and plays a key role in many cellular processes. 

Myosin-I molecules have several IQ sequences on or near the head and have light chains associated with them (Cheney and Mooseker, 1992 Cheney et al., 1993). Frequently, the light chains appear to be calmodulin molecules and some myosin-I molecules can bind three to four molecules of calmodulin at one time. Brush-border and adrenal myosin-I also bind calmodulin. Acanthamoeba myosin-I has a light chain that can be removed, in vitro, without adversely affecting the ATPase activity or the heavy chain phosphorylation (Korn and Hammer, 1988). The role of these calmodulin molecules in regulating myosin-I is complex and poorly understood. One possibility is that the calmodulin molecules dissociate from the heavy chains when calcium binds to the calmodulin, thereby imparting greater flexibility to the head of the myosin-I molecules. 

Single protein kinases such as PKA, PKC, and Ca +-calmodulin (CaM)-kinases, which result in the phosphorylation of serine and threonine residues in target proteins, play a very important role in hormone action. The discovery that the EGF receptor contains an intrinsic tyrosine kinase activity that is activated by the binding of the hgand EGF was an important breakthrough. The insuhn and IGF-I receptors also contain intrinsic... 

Calcineurin Cytosol A calmodulin-regulated protein phosphatase. May play important roles in cardiac hypertrophy and in regulating amounts of slow and fast twitch muscles. 

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. 

So far, it has been established from in vitro studies that the enzyme undergoes phosphorylation, a process that changes the conformation of the enzyme protein and leads to an increase in its activity. This involves Ca +/calmodulin-dependent protein kinase II and cAMP-dependent protein kinase which suggests a role for both intracellular Ca + and enzyme phosphorylation in the activation of tryptophan hydroxylase. Indeed, enzyme purified from brain tissue innervated by rostrally projecting 5-HT neurons, that have been stimulated previously in vivo, has a higher activity than that derived from unstimulated tissue but this increase rests on the presence of Ca + in the incubation medium. Also, when incubated under conditions which are appropriate for phosphorylation, the of tryptophan hydroxylase for its co-factor and substrate is reduced whereas its Fmax is increased unless the enzyme is purified from neurons that have been stimulated in vivo, suggesting that the neuronal depolarisation in vivo has already caused phosphorylation of the enzyme. This is supported by evidence that the enzyme activation caused by neuronal depolarisation is blocked by a Ca +/calmodulin protein kinase inhibitor. However, whereas depolarisation... 

Cheung, W.Y. Calmodulin plays a pivotal role in cellular regulation. Science. 207 19, 1980. 

The last phase of the excitotoxic cascade involves the activation of various biochemical pathways, among which phospholipases, proteases (in particular cal-pain), kinases and calmodulin-regulated enzymes such as nitric oxide synthase (NOS) play a prominent role. 

Table XI (346-390) lists a number of calcium-binding proteins and indicates very succinctly their role in biological systems. This table both illustrates the range of functions of calcium-binding proteins and serves to introduce those which appear subsequently in this chapter. The structures and functions of particularly important calcium-binding proteins such as calmodulin, parvalbumin, and troponin C are described in standard texts on biochemistry. The minimal Table XI entry for the particularly important calmodulins is amplified in the next paragraph. Table XI provides a sprinkling of references to enable readers to gain entry into the literature, for these and for most of the less-familiar species.

Although these two rate components can be identified in all nerves examined to date, the rates and the precise compositions varies among nerve populations. For example, SCa and SCb are readily resolved as discrete waves moving down optic axons, but differences in rate are smaller in the motor axons of sciatic nerve so the two peaks overlap. Moreover, virtually all tubulin moves as a single peak in SCa in optic axons, but significant amounts of tubulin move at both SCa and SCb rates in sciatic motor axons [32]. In each nerve, certain polypeptides may be used to define the kinetics for a given slow component of axonal transport. For SCa, those signature polypeptides are the NF triplet proteins, while actin, clathrin and calmodulin serve a similar role for SCb. 

The second myosin type identified in nervous tissue was the myosin I family. It was first described in protists and subsequently purified from brain. Myosin I is a singleheaded myosin with a short tail that uses calmodulin as a light chain [41]. In many cell types it has been implicated in both endocytosis and exocytosis, so it may play an important role in delivery and recycling of receptors. Myosin I is enriched in microvilli and may also be involved in some aspects of growth cone motility along with... 

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