B. Fuss et al., PHOSPHODIESTERASE-I, A NOVEL ADHESION MOLECULE AND OR CYTOKINE INVOLVED IN OLIGODENDROCYTE FUNCTION/, The Journal of neuroscience, 17(23), 1997, pp. 9095-9103
One of the more complex developmental processes occurring postnatally
in the CNS is the formation of the myelin sheath by oligodendrocytes.
To examine the molecular events that take place during myelination, we
isolated oligodendrocyte-derived cDNA clones, one of which (p421.HB)
represents a putative alternatively spliced isoform of rat brain-speci
fic phosphodiesterase I (PD-I alpha) and a species homolog of the huma
n cytokine autotaxin. Analysis of the structural composition of the p4
21.HB/PD-I alpha protein suggests a transmembrane-bound ectoenzyme, wh
ich, in addition to the phosphodiesterase-active site contains presume
d cell recognition and Ca2+-binding domains. Consequently, it may be i
nvolved in extracellular signaling events. Expression of p421.HB/PD-I
alpha is enriched in brain and spinal cord, where its mRNA can be dete
cted in oligodendrocytes and in cells of the choroid plexus. Expressio
n in the brain increases during development with an intermediate peak
of expression around the time of active myelination and maximal expres
sion in the adult. We have identified four presumably alternatively sp
liced isoforms, two of which appear to be CNS-specific. Decreased leve
ls of p421.HB/PD-I alpha mRNA in the dysmyelinating mouse mutant jimpy
, but not shiverer, suggest a role for p421.HB/PD-I alpha during activ
e myelination and/or late stages of oligodendrocyte differentiation. F
urthermore, p421.HB/PD-I alpha mRNA levels were reduced in the CNS at
onset of clinical symptoms in experimental autoimmune encephalomyeliti
s. These data together implicate the importance of p421.HB/PD-I alpha
in oligodendrocyte function, possibly through cell-cell and/or cell-ex
tracellular matrix recognition.