Fuss B, Baba H, Phan T, Tuohy V K, Macklin W B
Department of Neurosciences, Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
J Neurosci. 1997 Dec 1;17(23):9095-103. doi: 10.1523/JNEUROSCI.17-23-09095.1997.
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-Ialpha) and a species homolog of the human cytokine autotaxin. Analysis of the structural composition of the p421.HB/PD-Ialpha 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-Ialpha 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-Ialpha mRNA in the dysmyelinating mouse mutant jimpy, but not shiverer, suggest a role for p421.HB/PD-Ialpha during active myelination and/or late stages of oligodendrocyte differentiation. Furthermore, p421.HB/PD-Ialpha 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-Ialpha in oligodendrocyte function, possibly through cell-cell and/or cell-extracellular matrix recognition.
少突胶质细胞形成髓鞘是中枢神经系统（CNS）出生后发生的较为复杂的发育过程之一。为了研究髓鞘形成过程中发生的分子事件，我们分离了少突胶质细胞衍生的cDNA克隆，其中一个（p421.HB）代表大鼠脑特异性磷酸二酯酶I（PD-Iα）的一种假定的可变剪接异构体以及人类细胞因子自分泌运动因子的一个物种同源物。对p421.HB/PD-Iα蛋白结构组成的分析表明它是一种跨膜结合的胞外酶，除了磷酸二酯酶活性位点外，还包含推测的细胞识别和Ca2+结合结构域。因此，它可能参与细胞外信号事件。p421.HB/PD-Iα在脑和脊髓中表达丰富，其mRNA可在少突胶质细胞和脉络丛细胞中检测到。在发育过程中，脑中的表达增加，在活跃髓鞘形成期左右有一个表达的中间峰值，在成年期达到最大表达。我们已经鉴定出四种可能的可变剪接异构体，其中两种似乎是中枢神经系统特异性的。脱髓鞘小鼠突变体jimpy（而非颤抖小鼠）中p421.HB/PD-Iα mRNA水平降低，这表明p421.HB/PD-Iα在活跃髓鞘形成和/或少突胶质细胞分化后期发挥作用。此外，在实验性自身免疫性脑脊髓炎临床症状出现时，中枢神经系统中p421.HB/PD-Iα mRNA水平降低。这些数据共同表明p421.HB/PD-Iα在少突胶质细胞功能中具有重要性，可能是通过细胞间和/或细胞与细胞外基质的识别来实现的。
