Disruption of COPZ1-dependent retrograde Golgi-ER trafficking results in neutropenia. Vesicles containing different protein and lipid cargo flow back and forth between the Golgi and the ER. To sort the vesicles and deliver them to appropriate sites, coatomer complexes (such as COPI) are assembled on the vesicle surface. The COPI coatomer complex consists of 7 subunits. The ζ subunit (COPZ1) was found to be mutated in 3 children with symptomatic neutropenia from 2 unrelated families. The mutations cause instability of the COPI coatomer complex. Associated with this coatomer instability are changes in signaling pathways involving interferon (STING), interferon-stimulated genes (ISGs), and granulocyte colony-stimulating factor at the receptor level (G-CFSFR). Also affected are transcription factors NFκB and HIF-1α. Altogether, these changes affect inflammation, autophagy, and survival. C/EBPs, CCAAT/enhancer binding proteins; ROS, reactive oxygen species.

Disruption of COPZ1-dependent retrograde Golgi-ER trafficking results in neutropenia. Vesicles containing different protein and lipid cargo flow back and forth between the Golgi and the ER. To sort the vesicles and deliver them to appropriate sites, coatomer complexes (such as COPI) are assembled on the vesicle surface. The COPI coatomer complex consists of 7 subunits. The ζ subunit (COPZ1) was found to be mutated in 3 children with symptomatic neutropenia from 2 unrelated families. The mutations cause instability of the COPI coatomer complex. Associated with this coatomer instability are changes in signaling pathways involving interferon (STING), interferon-stimulated genes (ISGs), and granulocyte colony-stimulating factor at the receptor level (G-CFSFR). Also affected are transcription factors NFκB and HIF-1α. Altogether, these changes affect inflammation, autophagy, and survival. C/EBPs, CCAAT/enhancer binding proteins; ROS, reactive oxygen species.

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