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Murine SEC24D can substitute functionally for SEC24C during embryonic development.
Elizabeth J Adams1,2,3, Rami Khoriaty4,5,6,7, Anna Kiseleva1
1Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109, USA.
Scientific Reports
|October 27, 2021
Summary
The Sec24c and Sec24d proteins are crucial for early embryonic development. Replacing Sec24c with Sec24d allows survival to birth, suggesting expression timing, not cargo specificity, drives developmental roles.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- SEC24 proteins mediate cargo selection for COPII vesicle formation at the ER.
- Mammals have four SEC24 paralogs (Sec24a-d) in two subfamilies (SEC24A/B and SEC24C/D).
- SEC24C and SEC24D functions are poorly understood, with null mutations causing embryonic lethality.
Purpose of the Study:
- To investigate functional overlap and cargo specificity between SEC24C and SEC24D.
- To determine if SEC24C/D differences in cargo export explain their distinct embryonic lethality phenotypes.
Main Methods:
- Generated a Sec24cc-d allele using dual recombinase mediated cassette exchange.
- Replaced the C-terminal 90% of SEC24C with SEC24D coding sequence.
- Analyzed viability and developmental phenotypes of resulting Sec24cc-d/c-d mice.
Main Results:
- Sec24cc-d/c-d mice survived to term, unlike Sec24c nulls (lethal at E7.5).
- Sec24cc-d/c-d pups died shortly after birth and were smaller.
- No other obvious developmental abnormalities were noted in Sec24cc-d/c-d pups.
Conclusions:
- SEC24C and SEC24D likely possess similar cargo export functions.
- Tissue-specific and/or stage-specific expression patterns explain the critical roles of SEC24C and SEC24D in early embryogenesis.
