Abstract

Polysialic acid (polySia) attached to the neural cell adhesion molecule (NCAM) regulates inter alia the proliferation and differentiation via the interactions with neurotrophins. Since in postnatal epididymis neurotrophins and their receptors like the Low-Affinity Nerve Growth Factor Receptor p75 and TrK B receptor are expressed, we wanted to analyze if the polysialylation of NCAM is also involved during the development of the epididymis. To this end, we monitored the developmental changes in the expression of the polysialyltransferases and NCAM polysialylation using murine epididymis at different time points during postnatal development. Our results revealed that during postnatal development of the epididymis both polysialyltransferases, ST8SiaII and ST8SiaIV, were expressed and that the expression levels dropped with increasing age. In agreement with the expression levels of the polysialyltransferases the highest content of polysialylated NCAM was present during the first 10 days after birth. Interestingly, proliferating smooth muscle cell populations prevalently expressed polysialylated NCAM. Furthermore, we observed that inverse to the decrease in polysialylation of smooth muscle cells a strong up-regulation of collagen takes place suggesting a functional relationship since collagen was recently described to induce the turnover of polysialylated NCAM via an induction of endocytosis in cellulo. The same time course of polySia and collagen synthesis was also observed in other regions of the male reproductive system e.g. vas deferens and tunica albuginea (testis). Together, we identified a spatio-temporal expression pattern of polySia-NCAM characterized by high proliferation rate of smooth muscle cells and low collagen content.

Highlights

  • In mammals sialic acid polymers are present as posttranslational modification of distinct glycoproteins, whereupon the neuronal cell adhesion molecule neural cell adhesion molecule (NCAM) represents the major carrier of this strongly anionic charged carbohydrate epitope [1,2,3,4]

  • In the respiratory system polysialylated NCAM is released under inflammatory conditions and polysialic acid is proposed to counteract the cytotoxic properties of extracellular histones [16], which are accumulated during the formation of neutrophil extracellular traps (NET) [17,18]

  • Since polysialic acid (polySia) attached to NCAM influences the properties of neurotrophins [22,30], we analyzed the postnatal expression pattern of polysialylated NCAM in the postnatal epididymis

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Summary

Introduction

In mammals sialic acid polymers are present as posttranslational modification of distinct glycoproteins, whereupon the neuronal cell adhesion molecule NCAM represents the major carrier of this strongly anionic charged carbohydrate epitope [1,2,3,4]. A complex of polySia and bFGF leads to inhibition of bFGF-induced cell growth These different interplays may take part during testis development. The polysialylated form of NCAM is present during early testicular organogenesis on the cellular surface of Sertoli cells in addition to spermatogonia [21] and BDNF and other neurotrophins were described to be expressed during testis development supporting seminiferous cord formation and the survival of germ cells [23]. Receptors for BDNF and NT-3 and other neurotrophins are reported to be expressed in α smooth muscle isoactin (SMA) positive mesenchymal cells during postnatal development of epididymis [24] and an isoform of NCAM, not characterized in detail by these authors, was observed in postnatal epididymis [25]. Our results showing a time depending expression profile of polysialylated NCAM on SMA positive cells during a time window characterized by a high proliferation rate and low collagen expression

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