PUBLICATION
Functions of the COPII gene paralogs SEC23A and SEC23B are interchangeable in vivo
- Authors
- Khoriaty, R., Hesketh, G.G., Bernard, A., Weyand, A.C., Mellacheruvu, D., Zhu, G., Hoenerhoff, M.J., McGee, B., Everett, L., Adams, E.J., Zhang, B., Saunders, T.L., Nesvizhskii, A.I., Klionsky, D.J., Shavit, J.A., Gingras, A.C., Ginsburg, D.
- ID
- ZDB-PUB-180802-3
- Date
- 2018
- Source
- Proceedings of the National Academy of Sciences of the United States of America 115(33): E7748-E7757 (Journal)
- Registered Authors
- Ginsburg, David, Shavit, Jordan, Weyand, Angela
- Keywords
- SEC23, endoplasmic reticulum, mice, transgenic, vesicular transport proteins
- MeSH Terms
-
- Anemia, Dyserythropoietic, Congenital/genetics
- Anemia, Dyserythropoietic, Congenital/metabolism
- Bone Marrow/metabolism
- Bone Marrow/pathology
- COP-Coated Vesicles/genetics
- COP-Coated Vesicles/metabolism*
- Erythrocytes/metabolism*
- Erythrocytes/pathology
- Gene Expression Regulation
- HEK293 Cells
- Humans
- Multiprotein Complexes/biosynthesis*
- Multiprotein Complexes/genetics
- Species Specificity
- Vesicular Transport Proteins/biosynthesis*
- Vesicular Transport Proteins/genetics
- PubMed
- 30065114 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Khoriaty, R., Hesketh, G.G., Bernard, A., Weyand, A.C., Mellacheruvu, D., Zhu, G., Hoenerhoff, M.J., McGee, B., Everett, L., Adams, E.J., Zhang, B., Saunders, T.L., Nesvizhskii, A.I., Klionsky, D.J., Shavit, J.A., Gingras, A.C., Ginsburg, D. (2018) Functions of the COPII gene paralogs SEC23A and SEC23B are interchangeable in vivo. Proceedings of the National Academy of Sciences of the United States of America. 115(33):E7748-E7757.
Abstract
Approximately one-third of the mammalian proteome is transported from the endoplasmic reticulum-to-Golgi via COPII-coated vesicles. SEC23, a core component of coat protein-complex II (COPII), is encoded by two paralogous genes in vertebrates (Sec23a and Sec23b). In humans, SEC23B deficiency results in congenital dyserythropoietic anemia type-II (CDAII), while SEC23A deficiency results in a skeletal phenotype (with normal red blood cells). These distinct clinical disorders, together with previous biochemical studies, suggest unique functions for SEC23A and SEC23B. Here we show indistinguishable intracellular protein interactomes for human SEC23A and SEC23B, complementation of yeast Sec23 by both human and murine SEC23A/B, and rescue of the lethality of sec23b deficiency in zebrafish by a sec23a-expressing transgene. We next demonstrate that a Sec23a coding sequence inserted into the murine Sec23b locus completely rescues the lethal SEC23B-deficient pancreatic phenotype. We show that SEC23B is the predominantly expressed paralog in human bone marrow, but not in the mouse, with the reciprocal pattern observed in the pancreas. Taken together, these data demonstrate an equivalent function for SEC23A/B, with evolutionary shifts in the transcription program likely accounting for the distinct phenotypes of SEC23A/B deficiency within and across species, a paradigm potentially applicable to other sets of paralogous genes. These findings also suggest that enhanced erythroid expression of the normal SEC23A gene could offer an effective therapeutic approach for CDAII patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping