Unit of Biotechnology, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Unit of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Int J Mol Sci. 2023 Sep 1;24(17):13578. doi: 10.3390/ijms241713578.
Sialidases remove terminal sialic acids residues from the non-reducing ends of glycoconjugates. They have been recognized as catabolic enzymes that work within different subcellular compartments and can ensure the proper turn-over of glycoconjugates. Four mammalian sialidases (NEU1-4) exist, with different subcellular localization, pH optimum and substrate specificity. In zebrafish, seven different sialidases, with high homology to mammalian counterparts, have been identified. Zebrafish Neu3.2 is similar to the human cytosolic sialidase NEU2, which is involved in skeletal muscle differentiation and exhibits a broad substrate specificity toward gangliosides and glycoproteins. In zebrafish , mRNA is expressed during somite development, and its enzymatic activity has been detected in the skeletal muscle and heart of adult animals. In this paper, 1-4-cell-stage embryos injected with splice-blocking morpholino showed severe embryonic defects, mainly in somites, heart and anterior-posterior axis formation. and expressions were altered in morphants, and impaired musculature formation was associated with a defective locomotor behavior. Finally, the co-injection of mouse mRNA in morphants rescued the phenotype. These data are consistent with the involvement of cytosolic sialidase in pathologies related to muscle formation and support the validity of the model to investigate the pathogenesis of the diseases.
唾液酸酶从糖缀合物的非还原末端去除末端唾液酸残基。它们已被认为是在不同的亚细胞隔室中起作用的分解代谢酶，并且可以确保糖缀合物的适当转化。存在四种哺乳动物唾液酸酶（NEU1-4），具有不同的亚细胞定位、最适 pH 值和底物特异性。在斑马鱼中，已经鉴定出七种与哺乳动物具有高度同源性的不同唾液酸酶。斑马鱼 Neu3.2 类似于人类胞质唾液酸酶 NEU2，后者参与骨骼肌分化，并对神经节苷脂和糖蛋白表现出广泛的底物特异性。在斑马鱼中，mRNA 在体节发育过程中表达，并且其酶活性已在成年动物的骨骼肌和心脏中检测到。在本文中，注射了剪接阻断型 morpholino 的 1-4 细胞期胚胎表现出严重的胚胎缺陷，主要是在体节、心脏和前后轴形成中。在形态发生缺陷中， 和 的表达发生改变，并且肌肉形成受损与运动行为缺陷相关。最后，在形态发生缺陷中共同注射 小鼠 mRNA 可挽救表型。这些数据表明细胞质唾液酸酶参与与肌肉形成相关的病理学，并支持该模型用于研究疾病的发病机制的有效性。
