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Volume 17, Number 23,
Issue of December 1, 1997
pp. 9095-9103
Phosphodiesterase I, A Novel Adhesion Molecule and/or Cytokine
Involved in Oligodendrocyte Function
Received June 30, 1997; revised Aug. 28, 1997; accepted Sept. 11, 1997.
Babette Fuss1,
Hiroko Baba3,
Tom Phan1,
Vincent K. Tuohy2, and
Wendy B. Macklin1
Departments of 1 Neurosciences and
2 Immunology, Research Institute, The Cleveland Clinic
Foundation, Cleveland, Ohio 44195, and 3 National Institute
for Physiological Sciences, Okazaki, Aichi 444, Japan
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-specific phosphodiesterase I (PD-I ) and a
species homolog of the human cytokine autotaxin. Analysis of the
structural composition of the p421.HB/PD-I protein suggests a
transmembrane-bound ectoenzyme, which, in addition to the
phosphodiesterase-active site contains presumed cell recognition and
Ca2+-binding domains. Consequently, it may be
involved in extracellular signaling events. Expression of
p421.HB/PD-I is enriched in brain and spinal cord, where its mRNA
can be detected in oligodendrocytes and in cells of the choroid plexus.
Expression in the brain increases during development with an
intermediate peak of expression around the time of active myelination
and maximal expression in the adult. We have identified four presumably
alternatively spliced isoforms, two of which appear to be CNS-specific.
Decreased levels of p421.HB/PD-I mRNA in the
dysmyelinating mouse mutant jimpy, but not
shiverer, suggest a role for p421.HB/PD-I during
active myelination and/or late stages of oligodendrocyte
differentiation. Furthermore, p421.HB/PD-I mRNA levels were reduced
in the CNS at onset of clinical symptoms in experimental autoimmune
encephalomyelitis. These data together implicate the importance of
p421.HB/PD-I in oligodendrocyte function, possibly through
cell-cell and/or cell-extracellular matrix recognition.
Key words:
phosphodiesterase;
oligodendrocyte;
myelin;
cell
adhesion;
cytokine;
EAE
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