Berger U V, Schwab M E
Laboratory of Molecular and Developmental Neuroscience, Massachusetts General Hospital East, Charlestown 02129, USA.
J Neurocytol. 1996 Sep;25(9):499-512. doi: 10.1007/BF02284818.
N-Acetylated alpha-linked acidic dipeptidase is a membrane-bound peptidase that cleaves the neuropeptide N-acetyl-aspartyl-glutamate to N-acetyl-aspartate and glutamate. Previously, we have shown that in adult rat this enzyme is expressed by the non-myelinating Schwann cells in peripheral nerve. In the present study, we have determined the expression pattern of this peptidase in rat sciatic nerve during late embryonal and early postnatal development, using double-label immunofluorescence, enzyme assays and immunoblotting. We demonstrate that N-acetylated alpha-linked acidic dipeptidase is expressed by all Schwann cell precursor cells on embryonal day 14/15 and by all undifferentiated Schwann cells on embryonal days 16/17 and 20/21 and postnatal day 1. Moreover, we show that during the first postnatal week, the peptidase expression is down-regulated in the myelinating Schwann cells while the total enzyme activity levels and the enzyme amounts present in the nerve are transiently increased. To determine whether Schwann cell peptidase expression is dependent on axonal contact, we performed immunofluorescence experiments in cultured Schwann cells. These in vitro experiments demonstrate that the expression of this enzyme is maintained in culture for several weeks without axonal contact. Furthermore, they confirm previous suggestions that this peptidase is expressed on the extracellular side of the Schwann cell membrane. These findings support the notion that N-acetylated alpha-linked acidic dipeptidase takes part in signaling between peripheral axons and Schwann cells. The temporary increase in peptidase activity during the first postnatal week strongly implicates a role for this enzyme in the process of axon ensheathment and/or axon myelination.
N - 乙酰化α - 连接酸性二肽酶是一种膜结合肽酶，可将神经肽N - 乙酰天冬氨酰 - 谷氨酸裂解为N - 乙酰天冬氨酸和谷氨酸。此前，我们已经表明，在成年大鼠中，这种酶由外周神经中的非髓鞘形成雪旺细胞表达。在本研究中，我们使用双标记免疫荧光、酶活性测定和免疫印迹法，确定了这种肽酶在大鼠坐骨神经胚胎后期和出生后早期发育过程中的表达模式。我们证明，N - 乙酰化α - 连接酸性二肽酶在胚胎第14/15天由所有雪旺细胞前体细胞表达，在胚胎第16/17天、20/21天和出生后第1天由所有未分化的雪旺细胞表达。此外，我们表明，在出生后的第一周，髓鞘形成雪旺细胞中的肽酶表达下调，而神经中存在的总酶活性水平和酶量则短暂增加。为了确定雪旺细胞肽酶的表达是否依赖于轴突接触，我们在培养的雪旺细胞中进行了免疫荧光实验。这些体外实验表明，在没有轴突接触的情况下，这种酶的表达在培养物中维持了数周。此外，它们证实了先前的推测，即这种肽酶在雪旺细胞膜的细胞外侧表达。这些发现支持了N - 乙酰化α - 连接酸性二肽酶参与外周轴突与雪旺细胞之间信号传导的观点。出生后第一周肽酶活性的暂时增加强烈暗示了这种酶在轴突包裹和/或轴突髓鞘形成过程中的作用。
