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The Calcium-Calmodulin System
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
The physiological activities of calmodulin are regulated by calmodulin-binding proteins that are frequently associated with particular cytoskeletal components. These regulatory proteins include caldesmon, calcineurin, calspectin and spectin, as well as the microtubule-associated protein 2 (MAP-2) and cytosynalin. The 35-kDa protein, cytosynalin, purified from synaptosomal membranes, has a broad range of interactions with cytoskeletal elements.225 Cytosynalin is linked to calspectin on the inner aspect of the membrane and may interact with actin filaments or microtubules.
Stimulus-Secretion Coupling: Intracellular Proteins and Nucleotides
Published in Stephen W. Carmichael, Susan L. Stoddard, The Adrenal Medulla 1986 - 1988, 2017
Stephen W. Carmichael, Susan L. Stoddard
The presence of calmodulin-binding proteins in three neurosecretory vesicles (bovine adrenal chromaffin vesicles, bovine posterior pituitary secretory vesicles, and rat brain synaptic vesicles) was investigated by Fournier and Trifard (1988a). When detergent-solubilized membrane proteins from each type of organelle were applied to calmodulin-affinity columns in the presence of calcium, several calmodulin-binding proteins were retained. In all three membranes, proteins of about 65 kDa and 53 kDa were found consistently. Two monoclonal antibodies previously shown to react with a cholinergic vesicle membrane protein were reactive with the 65 kDa protein present in chromaffin vesicle membranes. These and other results clearly indicate that an immunologically identical calmodulin-binding protein is expressed in at least three different neurosecretory vesicle types, thus suggesting a common role for this protein in secretory vesicle function.
Role of cAMP, Calcium, and Protein Phosphorylation in Sperm Motility
Published in Claude Gagnon, Controls of Sperm Motility, 2020
Calmodulin is a prominent candidate as the signal transducer in calcium-regulated motility. Calmodulin is present in flagella and cilia,13,44 yet a clear understanding of its role in flagellar motility has been conspicuously elusive. A function for calmodulin was suggested by waveform changes resulting from anticalmodulin drug treatment in live cells.38,45 A general problem probing calmodulin action has been that effects of anticalmodulin drugs were usually severely attenuated when reactivated models were tested. Nonetheless, the effects observed by these drugs were consistent with the concept that the effects of calcium were transduced through calmodulin. Inhibitory effects of calcium on protein phosphorylation catalyzed by cAMP in reactivated dog sperm have been noted (Figure 2). These calcium-dependent effects were found to be blocked by anticalmodulin drugs. Attempts to demonstrate a direct association of calmodulin with dynein have yielded conflicting results.44,46 The high molar ratios of calmodulin to dynein required to alter dynein ATPase47 activity suggest either that the conditions of axoneme or dynein preparation pivotal to preserving such an interaction have not been optimized or that calmodulin may regulate motility through an indirect interaction with dynein via another component. Both possibilities are supported by data collected thus far. Evidence for an intermediate calmodulin-regulated component has been obtained by the identification of a variety of calmodulin-binding proteins in sperm and other types of flagella.48-51 The pattern of binding proteins obtained varies markedly with species and sample preparation. The interpretation of results obtained by overlay after SDS-denaturation must be viewed in light of the fact that calmodulin can bind in a calcium-dependent manner to abundant hydrophobic domains in substances that are not physiologically relevant.52,53 Under such conditions, less abundant regulatory components might be undetected. With respect to optimization of conditions for binding in situ, Brokaw and Nagayama54 found that the ability to confer asymmetry by calmodulin depended upon the calcium environment at the time of permeabilization. If cells were lysed in the presence of calcium, then addition of calcium-calmodulin-produced asymmetric waveform. Conversely, when lysed in the absence of calcium, subsequent reactivation was not responsive to calcium-calmodulin. The suggestion that some of these proteins are, in turn, calmodulin-binding proteins is consistent with our observation that the ability to regulate reactivated sperm movement by calcium, calmodulin, or calmodulin-dependent protein phosphatase was enhanced markedly when inhibitors of trypsin are included. Most calmodulin-binding proteins are extremely sensitive to trypsin digestion, including the calmodulin-dependent protein phosphatase.55
The role of synaptic biomarkers in the spectrum of neurodegenerative diseases
Published in Expert Review of Proteomics, 2020
Sonia Mazzucchi, Giovanni Palermo, Nicole Campese, Alessandro Galgani, Alessandra Della Vecchia, Andrea Vergallo, Gabriele Siciliano, Roberto Ceravolo, Harald Hampel, Filippo Baldacci
Ng is a 78 aa neuron-specific post-synaptic somato-dendritic protein. It is one of the most abundant calmodulin-binding proteins and is mainly expressed by excitatory neurons of the cerebral cortex and hippocampus. High levels can be measured in amygdala, caudate, and putamen, whereas it is poorly expressed or absent in other brain regions as the thalamus, cerebellum, brainstem, and the spinal cord [5]. The protein can be found in neurons but is not expressed by glial cells. Ng regulates synaptic activity, mainly LTP, through its binding to calmodulin that is increased in the presence of low calcium concentrations and inhibited by large calcium amounts. In animal models, Ng overexpression demonstrated to enhance LTP and improve cognitive performances, whereas in Ng knockout mice memory deficits were reported, probably due to an impairment or even a block of LTP [8]. Furthermore, preclinical studies highlighted an age-dependent reduction of Ng mRNA in several brain regions, including the hippocampus [28].
Relationship between uterine smooth muscular CPI-17-signal pathway-mediated Ca2+ sensitivity changes and uterine atony-induced postpartum haemorrhage
Published in Journal of Obstetrics and Gynaecology, 2019
Qiuping Liao, Jianying Yan, Zhimei Zhou, Jinying Luo, Qing Han, Qinjian Zhang, Rongxin Chen
This study showed that the expression of USM p-CPI-17 (Thr38) protein in the case group was significantly lower than that of the control group. The expression levels of p-CPI-17 (Thr38) protein of the two groups were closely related to the activities of USM contraction and the 24 h PPH volumes, suggesting that the reduction of p-CPI-17 (Thr38) protein expression could lead to the weakening of USM contraction activity, causing an increase of PPH volume. This result was similar to Lartey et al.’s findings (2007); this study found that the expression of phosphorylated CPI-17 protein was significantly lower than the non-pregnant USM, while it increased when in preterm labour, suggesting that CPI-17 would promote the uterine contraction, thus launching childbirth. The multidimensional nuclear magnetic resonance (NMR) spectroscopy technology showed the position of phosphorylated 38th threonine would change, inducing the swing of the phosphate-binding loop and the formation of hydrophobic core; thus the phosphorylated residues would be exposed on the protein surface, limiting the hydrolysis of myosin light chain phosphatase (MLCP). This increases its inhibition ability by 1000 times (Eto et al. 2007). In addition to the MLCP activity inhibition, the phosphorylated CPI-17 could also interact with the calmodulin binding protein (Xiao et al. 2005), eliminating the inhibitory effect towards the actin ATPase. This means it reduces the inhibition towards the smooth muscular contraction, and increases the muscular sensitivity towards Ca2+, and regulates the stress fibre formation (Paula et al. 2011). This starts the dissociation and re-assembly of the actin and myosin and the remodelling of the cytoskeleton, thus affecting the smooth muscle contraction. The above studies co-indicated that the phosphorylated CPI-17 would regulate and enhance the USM Ca2+ sensitivity. The CPI 17-expression was not detected inside the chicken’s arterial smooth muscle; the agonists could not stimulate the contraction (Kitazawa et al. 2004). Therefore, CPI-17 was the determinant key of agonist-induced smooth muscular contraction. The oxytocin and endothelin were the effective uterotonic, which could stimulate the CPI-17 phosphorylation (Lartey et al. 2007; Sakai et al. 2007), indicating that they might be involved in the possible molecular mechanism of promoting childbirth and treating PPH.