Thompson George, Hoyle Anna, Lewis Philip A, Prada-Sanchez M Esther, Swift Joe, Heesom Kate, Lowe Martin, Stephens David, Stevenson Nicola L
School of Biochemistry, University of Bristol , Bristol, England.
Wellcome Centre for Cell-Matrix Research , Manchester, UK.
J Cell Biol. 2025 Oct 6;224(10). doi: 10.1083/jcb.202411167. Epub 2025 Aug 18.
The secretion of extracellular matrix (ECM) proteins is vital to the maintenance of tissue health. One major control point of this process is the Golgi apparatus, whose dysfunction causes numerous connective tissue disorders. We therefore sought to investigate the role of two Golgi organizing proteins, GMAP210 and Golgin-160, in ECM secretion. CRISPR knockout of either protein had distinct impacts on Golgi organization, with Golgin-160 knockout causing Golgi fragmentation and vesicle accumulation, and GMAP210 loss leading to cisternal fragmentation, dilation, and the accumulation of tubulovesicular structures. Both golgins were required for fibrillar collagen organization and glycosaminoglycan synthesis suggesting nonredundant functions in these processes. Furthermore, proteomics analysis revealed both shared and golgin-specific changes in the secretion of ECM proteins. We therefore propose that golgins are collectively required to create the correct physical-chemical space to support efficient ECM protein secretion, modification, and assembly. This is the first time that Golgin-160 has been shown to be required for ECM secretion.
细胞外基质（ECM）蛋白的分泌对于维持组织健康至关重要。这一过程的一个主要控制点是高尔基体，其功能障碍会导致多种结缔组织疾病。因此，我们试图研究两种高尔基体组织蛋白GMAP210和高尔基体蛋白160在ECM分泌中的作用。对这两种蛋白中的任何一种进行CRISPR基因敲除都会对高尔基体组织产生不同的影响，高尔基体蛋白160基因敲除会导致高尔基体碎片化和囊泡积累，而GMAP210缺失会导致扁平囊碎片化、扩张以及小管泡状结构的积累。这两种高尔基体蛋白对于纤维状胶原蛋白的组织和糖胺聚糖的合成都是必需的，表明它们在这些过程中具有非冗余功能。此外，蛋白质组学分析揭示了ECM蛋白分泌中共同的和高尔基体蛋白特异性的变化。因此，我们提出，高尔基体蛋白共同作用以创造正确的物理化学空间，以支持高效的ECM蛋白分泌、修饰和组装。这是首次表明高尔基体蛋白160是ECM分泌所必需的。
