PHOSPHODIESTERASE-I, A NOVEL ADHESION MOLECULE AND OR CYTOKINE INVOLVED IN OLIGODENDROCYTE FUNCTION/

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.