Departamento de Bioquímica, Instituto de Farmacologia e Biologia Molecular, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100, São Paulo, SP 04044-020, Brazil.
Departamento de Bioquímica, Instituto de Farmacologia e Biologia Molecular, Escola Paulista de Medicina, Universidade Federal de São Paulo, Rua Três de Maio, 100, São Paulo, SP 04044-020, Brazil; Department of Biochemistry and Systems Biology, ISMIB, University of Liverpool, Liverpool, L69 7ZB, UK.
Carbohydr Polym. 2021 Mar 1;255:117477. doi: 10.1016/j.carbpol.2020.117477. Epub 2020 Dec 3.
The cell surface and extracellular matrix polysaccharide, heparan sulfate (HS) conveys chemical information to control crucial biological processes. HS chains are synthesized in a non-template driven process mainly in the Golgi apparatus, involving a large number of enzymes capable of subtly modifying its substitution pattern, hence, its interactions and biological effects. Changes in the localization of HS-modifying enzymes throughout the Golgi were found to correlate with changes in the structure of HS, rather than protein expression levels. Following BFA treatment, the HS-modifying enzymes localized preferentially in COPII vesicles and at the trans-Golgi. Shortly after heparin treatment, the HS-modifying enzyme moved from cis to trans-Golgi, which coincided with increased HS sulfation. Finally, it was shown that COPI subunits and Sec24 gene expression changed. Collectively, these findings demonstrate that knowledge of the ER-Golgi dynamics of HS-modifying enzymes via vesicular trafficking is a critical prerequisite for the complete delineation of HS biosynthesis.
细胞表面和细胞外基质多糖，硫酸乙酰肝素 (HS) 向控制关键生物过程的化学信息。HS 链是在非模板驱动的过程中主要在高尔基体中合成的，涉及许多能够微妙修饰其取代模式的酶，因此，它的相互作用和生物学效应。在整个高尔基体中 HS 修饰酶的定位变化被发现与 HS 结构的变化相关，而不是蛋白质表达水平。在用 BFA 处理后，HS 修饰酶优先定位于 COPII 小泡和反式高尔基体。肝素处理后不久，HS 修饰酶从顺式高尔基体转移到反式高尔基体，这与 HS 硫酸化程度的增加相一致。最后，证明 COPI 亚基和 Sec24 基因表达发生了变化。总之，这些发现表明，通过囊泡运输了解 HS 修饰酶的 ER-Golgi 动力学是完整描绘 HS 生物合成的关键前提。
