Expression of neuroserpin, an inhibitor of tissue plasminogen activator, in the developing and adult nervous system of the mouse

J Neurosci. 1997 Dec 1;17(23):8984-96. doi: 10.1523/JNEUROSCI.17-23-08984.1997.

Abstract

Neuroserpin is a serine protease inhibitor of the serpin family that has been identified as an axonally secreted glycoprotein in neuronal cultures of chicken dorsal root ganglia. To obtain an indication for possible functions of neuroserpin, we analyzed its expression in the developing and the adult CNS of the mouse. In the adult CNS, neuroserpin was most strongly expressed in the neocortex, the hippocampal formation, the olfactory bulb, and the amygdala. In contrast, most thalamic nuclei, the caudate putamen, and the cerebellar granule cells were devoid of neuroserpin mRNA. During embryonic development, neuroserpin mRNA was not detectable in neuroepithelia, but it was expressed in the differentiating fields of most CNS regions concurrent with their appearance. In the cerebellum, the granule cells and a subgroup of Purkinje cells were neuroserpin-positive during postnatal development. As a further step toward the elucidation of neuroserpin function, we performed a study to identify potential target proteases. In vitro, neuroserpin formed SDS-stable complexes and inhibited the amidolytic activity of tissue plasminogen activator, urokinase, and plasmin. In contrast, no complex formation with or inhibition of thrombin was found. Expression pattern and inhibitory specificity implicate neuroserpin as a candidate regulator of plasminogen activators, which have been suggested to participate in the modulation or reorganization of synaptic connections in the adult. During development, neuroserpin may attenuate extracellular proteolysis related to processes such as neuronal migration, axogenesis, or the formation of mature synaptic connections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Axons / physiology
  • Base Sequence
  • Brain / embryology
  • Brain / growth & development
  • Brain / metabolism
  • Central Nervous System / embryology
  • Central Nervous System / growth & development
  • Central Nervous System / metabolism*
  • Fetal Proteins / biosynthesis*
  • Fetal Proteins / genetics
  • Fetal Proteins / physiology
  • Fibrinolysin / antagonists & inhibitors
  • Gene Expression Regulation, Developmental*
  • Genes
  • In Situ Hybridization
  • Mice
  • Mice, Inbred ICR
  • Molecular Sequence Data
  • Neuronal Plasticity / physiology
  • Neuropeptides / biosynthesis*
  • Neuropeptides / genetics
  • Neuropeptides / pharmacology
  • Neuropeptides / physiology
  • Organ Specificity
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / pharmacology
  • Serine Proteinase Inhibitors / genetics
  • Serine Proteinase Inhibitors / physiology
  • Serpins / biosynthesis*
  • Serpins / genetics
  • Serpins / pharmacology
  • Serpins / physiology
  • Synapses / physiology
  • Synaptic Transmission / drug effects
  • Thrombin / antagonists & inhibitors
  • Tissue Plasminogen Activator / antagonists & inhibitors*

Substances

  • Fetal Proteins
  • Neuropeptides
  • Recombinant Fusion Proteins
  • Serine Proteinase Inhibitors
  • Serpins
  • neuroserpin
  • Thrombin
  • Tissue Plasminogen Activator
  • Fibrinolysin

Associated data

  • GENBANK/AJ001700