Sr. Krueger et al., EXPRESSION OF NEUROSERPIN, AN INHIBITOR OF TISSUE-PLASMINOGEN ACTIVATOR, IN THE DEVELOPING AND ADULT NERVOUS-SYSTEM OF THE MOUSE, The Journal of neuroscience, 17(23), 1997, pp. 8984-8996
Neuroserpin is a serine protease inhibitor of the serpin family that h
as been identified as an axonally secreted glycoprotein in neuronal cu
ltures of chicken dorsal root ganglia. To obtain an indication for pos
sible functions of neuroserpin, we analyzed its expression in the deve
loping and the adult CNS of the mouse. In the adult CNS, neuroserpin w
as most strongly expressed in the neocortex, the hippocampal formation
, the olfactory bulb, and the amygdala. In contrast, most thalamic nuc
lei, the caudate putamen, and the cerebellar granule cells were devoid
of neuroserpin mRNA. During embryonic development, neuroserpin mRNA w
as not detectable in neuroepithelia, but it was expressed in the diffe
rentiating fields of most CNS regions concurrent with their appearance
. In the cerebellum, the granule cells and a subgroup of Purkinje cell
s were neuroserpin-positive during postnatal development. As a further
step toward the elucidation of neuroserpin function, we performed a s
tudy to identify potential target proteases. In vitro, neuroserpin for
med SDS-stable complexes and inhibited the amidolytic activity of tiss
ue plasminogen activator, urokinase, and plasmin. In contrast, no comp
lex formation with or inhibition of thrombin was found. Expression pat
tern and inhibitory specificity implicate neuroserpin as a candidate r
egulator of plasminogen activators, which have been suggested to parti
cipate 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, axogenes
is, or the formation of mature synaptic connections.