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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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