Open AccessCompetitive Tuning Among Ca2+/Calmodulin-Dependent Proteins: Analysis of In Silico Model Robustness and Parameter Variability
Author(s) -
Matthew C Pharris,
Neal M. Patel,
Tamara L. KinzerUrsem
Publication year - 2018
Publication title -
cellular and molecular bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.668
H-Index - 34
eISSN - 1865-5033
pISSN - 1865-5025
DOI - 10.1007/s12195-018-0549-4
Subject(s) - calmodulin , microbiology and biotechnology , in silico , synaptic plasticity , calcium signaling , biology , signal transduction , robustness (evolution) , phosphatase , receptor , chemistry , neuroscience , biochemistry , phosphorylation , gene , enzyme
Calcium/Calmodulin-dependent (Ca 2+ /CaM-dependent) regulation of protein signaling has long been recognized for its importance in a number of physiological contexts. Found in almost all eukaryotic cells, Ca 2+ /CaM-dependent signaling participates in muscle development, immune responses, cardiac myocyte function and regulation of neuronal connectivity. In excitatory neurons, dynamic changes in the strength of synaptic connections, known as synaptic plasticity, occur when calcium ions (Ca 2+ ) flux through NMDA receptors and bind the Ca 2+ -sensor calmodulin (CaM). Ca 2+ /CaM, in turn, regulates downstream protein signaling in actin polymerization, receptor trafficking, and transcription factor activation.The activation of downstream Ca 2+ /CaM-dependent binding proteins (CBPs) is a function of the frequency of Ca 2+ flux, such that each CBP is preferentially "tuned" to different Ca 2+ input signals. We have recently reported that competition among CBPs for CaM binding is alone sufficient to recreate in silico the observed in vivo frequency-dependence of several CBPs. However, CBP activation may strongly depend on the identity and concentration of proteins that constitute the competitive pool; with important implications in the regulation of CBPs in both normal and disease states.