Format

Send to

Choose Destination
Curr Biol. 2015 Feb 16;25(4):403-12. doi: 10.1016/j.cub.2014.11.070. Epub 2015 Jan 22.

Sec24 is a coincidence detector that simultaneously binds two signals to drive ER export.

Author information

1
Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: sp2430@columbia.edu.
2
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
3
Department of Biological Sciences, Columbia University, New York, NY 10027, USA. Electronic address: em2282@columbia.edu.

Abstract

BACKGROUND:

Incorporation of secretory proteins into ER-derived vesicles involves recognition of cytosolic signals by the COPII coat protein, Sec24. Additional cargo diversity is achieved through cargo receptors, which include the Erv14/Cornichon family that mediates export of transmembrane proteins despite the potential for such clients to directly interact with Sec24. The molecular function of Erv14 thus remains unclear, with possible roles in COPII binding, membrane domain chaperoning, and lipid organization.

RESULTS:

Using a targeted mutagenesis approach to define the mechanism of Erv14 function, we identify conserved residues in the second transmembrane domain of Erv14 that mediate interaction with a subset of Erv14 clients. We further show that interaction of Erv14 with a novel cargo-binding surface on Sec24 is necessary for efficient trafficking of all of its clients. However, we also determine that some Erv14 clients also directly engage an adjacent cargo-binding domain of Sec24, suggesting a novel mode of dual interaction between cargo and coat.

CONCLUSIONS:

We conclude that Erv14 functions as a canonical cargo receptor that couples membrane proteins to the COPII coat, but that maximal export requires a bivalent signal that derives from motifs on both the cargo protein and Erv14. Sec24 can thus be considered a coincidence detector that binds simultaneously to multiple signals to drive packaging of polytopic membrane proteins. This mode of dual signal binding to a single coat protein might serve as a general mechanism to trigger efficient capture, or may be specifically employed in ER export to control deployment of nascent proteins.

PMID:
25619760
PMCID:
PMC4334704
DOI:
10.1016/j.cub.2014.11.070
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center