The N‐terminal domain of the myelin enzyme 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase: direct molecular interaction with the calcium sensor calmodulin
Copyright policy )The N‐terminal domain of the myelin enzyme 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase: direct molecular interaction with the calcium sensor calmodulin
Abstract2′,3′‐cyclic nucleotide 3′‐phosphodiesterase (CNPase) is a quantitatively major enzyme in myelin, where it localizes to the non‐compact regions and is bound to the membrane surface. Although its catalytic activity in vitro has been characterized, the physiological function and in vivo substrate of CNPase remain unknown. Especially the N‐terminal domain has been poorly characterized; previously, we have shown it is involved in CNPase dimerization and RNA binding. Here, we show that purified CNPase binds to the calcium sensor protein calmodulin (CaM) in a calcium‐dependent manner; the binding site is in the N‐terminal domain of CNPase. CaM does not affect the phosphodiesterase activity of CNPase in vitro, nor does it influence polyadenylic acid binding. The colocalization of CNPase and CaM during Schwann cell myelination in culture was observed, and CaM antagonists induced the colocalization of CNPase with microtubules in differentiated CG‐4 oligodendrocytes. An analysis of post‐translational modifications of CNPase from rat brain revealed the presence of two novel phosphorylation sites on Tyr110 and Ser169 within the N‐terminal domain. The results indicate a role for the N‐terminal domain of CNPase in mediating multiple molecular interactions and provide a starting point for detailed structure‐function studies on CNPase and its N‐terminal domain.
- Universität Hamburg Germany
- Medical University of Vienna Austria
- University of Oulu Finland
- Oulu University Hospital Finland
- Tokushima Bunri University Japan
Models, Molecular, Molecular Sequence Data, Brain, Embryo, Mammalian, Nerve Fibers, Myelinated, Chromatography, Affinity, Mice, Inbred C57BL, Mice, Oligodendroglia, Organ Culture Techniques, Calmodulin, 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase, Ganglia, Spinal, Chromatography, Gel, Animals, Humans, Enzyme Inhibitors, Phosphorylation, Protein Processing, Post-Translational, Protein Binding
Models, Molecular, Molecular Sequence Data, Brain, Embryo, Mammalian, Nerve Fibers, Myelinated, Chromatography, Affinity, Mice, Inbred C57BL, Mice, Oligodendroglia, Organ Culture Techniques, Calmodulin, 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase, Ganglia, Spinal, Chromatography, Gel, Animals, Humans, Enzyme Inhibitors, Phosphorylation, Protein Processing, Post-Translational, Protein Binding
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).20 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!