Endoplasmic reticulum export and early secretory pathway machinery (COPII machinery)

The endoplasmic reticulum (ER) export and early secretory pathway machinery is a complex system of proteins responsible for the transport of newly synthesized proteins and lipids from the ER to the Golgi apparatus. This process is primarily driven by the COPII (Coat Protein Complex II) machinery, which includes the small GTPase SAR1 and the heterotetrameric coat proteins SEC23/SEC24 and SEC13/SEC31 (PMID: 29454281). These components coordinate to select cargo, deform the ER membrane, and bud off transport vesicles at specialized regions called ER exit sites (ERES). Beyond its fundamental role in cellular homeostasis and protein secretion, this machinery is frequently hijacked by various viruses to facilitate their replication and assembly (PMID: 32814545). Dysregulation of the early secretory pathway is implicated in several human diseases, including rare genetic disorders like Cranio-lenticulo-sutural dysplasia and Chylomicron retention disease, which result from mutations in SEC23A and SAR1B, respectively (PMID: 16532009, 12529853). In oncology, the pathway is often upregulated to accommodate the increased secretory load of cancer cells, making it a potential therapeutic target (PMID: 28611164). While small molecules like Brefeldin A and FLI-06 are used to inhibit this pathway in laboratory settings, their high toxicity presents a significant challenge for clinical development. Current research focuses on identifying more selective inhibitors that can target specific isoforms or viral-specific interactions within the machinery to minimize systemic side effects.

Other names

COPII-mediated transportER-to-Golgi transportEarly secretory pathwayER export machineryER exit site machinery

Inhibition of COPII vesicle assembly, disruption of SAR1/ARF1 GTPase cycling, and blockade of cargo recruitment at ER exit sites (PMID: 23530179, 19433065).