Dataset Information

Golgin knockouts alter extracellular matrix secretion

ABSTRACT: The secretion of extracellular matrix (ECM) proteins is vital to the maintenance of tissue health. One 28 major control point of this process is the Golgi apparatus, whose dysfunction causes numerous 29 connective tissue disorders. Golgi function is tightly linked to its structure, which is maintained by the 30 cytoskeleton and Golgi organising proteins. We sought to investigate the role of two of these 31 organising proteins, the golgins GMAP210 and Golgin-160, in ECM secretion. We found that loss of 32 either protein had distinct impacts on Golgi organisation. GMAP210 loss caused cisternal 33 fragmentation and dilation, alongside the accumulation of tubulovesicular structures. Meanwhile, 34 Golgin-160 knockout lead to Golgi fragmentation and vesicle build-up. Nonetheless, loss of each 35 protein had a similar impact on ECM secretion and glycosaminoglycan synthesis. We therefore 36 propose that golgins are collectively required to create the correct physical-chemical space to 37 support efficient ECM protein secretion and modification. This is the first time that Golgin-160 has 38 been shown to be required for ECM secretion.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Anna Hoyle

LAB HEAD: Nicola Stevenson

PROVIDER: PXD061302 | Pride | 2025-08-25

REPOSITORIES: Pride

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Publications

Multiple golgins are required to support extracellular matrix secretion, modification, and assembly.

Thompson George G Hoyle Anna A Lewis Philip A PA Prada-Sanchez M Esther ME Swift Joe J Heesom Kate K Lowe Martin M Stephens David D Stevenson Nicola L NL

The Journal of cell biology 20250818 10

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 accumulatio ...[more]

PMID: 40824304

Similar Datasets

Project description:Protein secretion is an essential process in cell biology. The conventional secretion pathway is well known, and involves proteins with a signal sequence being directed into the endoplasmic reticulum. Once in the lumen of the endoplasmic reticulum, proteins are trafficked through the Golgi and remain separate from the cytosol throughout their journey to the outside of the cell. More recently, proteins without a signal sequence have been found outside the cell. These proteins are secreted unconventionally, and avoid the ER-Golgi route. For both pathways, some aspects remain unclear, particularly surrounding the regulation of protein secretion. Galectin-3, an unconventionally secreted protein, was used here to investigate both conventional and unconventional protein secretion. The unconventional protein secretion of galectin-3 is poorly understood. To address this, genetic manipulation of galectin-3 was used to gain insights into the mechanism of galectin-3 secretion. It was found that galectin-3 does not require unfolding or binding to cell surface glycoproteins to be secreted. Galectin-3 was also used to assess protein secretion using a genome-wide CRISPR screen. As galectin‑3 binds to cell surface glycoproteins, galectin-3 on the cell surface was used to assess secretion of these glycoproteins. Hits were validated by a glycoprotein secretion assay. Using this pipeline, 93 hits were identified as involved in protein secretion, of which 51 were novel hits not previously associated with protein secretion. Many of the hits identified also resulted in a phenotype of altered Golgi morphology, and five of these were investigated further. Two novel hits that localised to the Golgi were identified, TMEM220 and GPR161. GPR161 likely mediates its effect on Golgi morphology by its interaction with golgin A5. This thesis presents new insights into both conventional and unconventional protein secretion. Insights into the mechanism for galaectin-3 secretion were revealed. A novel Golgi-localised regulator of secretion, GRP161, was identified, with a mechanism for action suggested. Importantly, the list of 51 novel genes identified will serve as a useful resource for other researchers investigating protein secretion.

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