Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium concentrations as well as time courses have been used to model the signaling cascades leading to changes in the strength of synaptic connections. Previous models consider the dendritic spines as uniform compartments regarding calcium signaling. However, calcium concentrations can vary drastically on distances much smaller than typical spine sizes, and downstream targets of calcium signals are often found exactly in these calcium nanodomains. Even though most downstream targets are activated by calcium via calmodulin, which is a diffusive molecule, the capacity of calmodulin to bind to its targets even when it is not fully loaded with calcium allows its downstream cascade to be highly local. In this study, a model is proposed which uses the heterogeneity of calcium concentrations as a signal for spike-timing-dependent plasticity (STDP). The model is minimalistic and includes three sources of calcium in spines: NMDA receptors (NMDARs), voltage gated calcium channels (VGCCs) and IP3 receptors (IP3Rs). It is based on the biochemical cascades and assumption of spatial locations of four calcium-dependent enzymes: calcium/calmodulin-dependent protein kinase II located near NMDARs, calcineurin located near VGCCs, cyclic nucleotide phosphodiesterase (PDE) located near IP3Rs or NMDARs and adenylyl cyclase, located between VDCCs and NMDARs. To quantify the changes in synaptic weights the model also includes a simple description of AMPA receptor insertion in the membrane and docking to the postsynaptic density. Two parameters of the model are tuned such that weight changes produced by either pre or postsynaptic firing alone are minimal. The model reproduces the typical shape of STDP for spike doublets. If PDE is located near IP3Rs, the behavior for spike triplets is consistent with that observed in hippocampal cell culture; if near NMDAR, the behavior is similar to that observed in cortical L2/3 slices.
 ...
PMID:Calcium messenger heterogeneity: a possible signal for spike timing-dependent plasticity. 2125 20

Calmodulin(CaM)-dependent cyclic nucleotide phosphodiesterase (PDE1) plays a critical role in the complex interactions between the cyclic nucleotide and Ca(2+) second messenger systems. Bovine brain contains two major PDE1 isozymes, designated according to tissue origin and subunit molecular mass as brain 60 kDa and 63 kDa PDE1 isozymes. Kinetic properties suggest that 63 kDa PDE1 isozyme is distinct from 60 kDa, heart and lung PDE1 isozymes. Although 60 kDa, heart and lung PDE1 isozymes are almost identical in immunological properties, they are differentially activated by calmodulin (CaM). These isozymes are further distinguished by the effects of pharmacological agents. Another main difference is that 60 kDa PDE1 isozyme is a substrate of cAMP-dependent protein kinase, whereas, 63 kDa PDE1 isozyme is phosphorylated by CaM-dependent protein kinase. The phosphorylation of PDE1 isozymes is accompanied by a decrease in the isozyme affinity towards CaM, and it can be reversed by a CaM-dependent phosphatase (calcineurin). The complex regulatory properties of PDE1 isozymes are precisely regulated by cross-talk between the Ca(2+) and cAMP signaling pathways.
 ...
PMID:Diversity of calcium action in regulation of mammalian calmodulin-dependent cyclic nucleotide phosphodiesterase. 2290 Feb 95


<< Previous 1 2 3 4