The [corrected] SEC23-SEC31 [corrected] interface plays critical role for export of procollagen from the endoplasmic reticulum.
COPII proteins are essential for exporting most cargo molecules from the endoplasmic reticulum. The membrane-facing surface of the COPII proteins (especially SEC23-SEC24) interacts directly or indirectly with the cargo molecules destined for exit. As we characterized the SEC23A mutations at the SEC31 binding site identified from patients with cranio-lenticulo-sutural dysplasia, we discovered that the SEC23-SEC31 interface can also influence cargo selection. Remarkably, M702V SEC23A does not compromise COPII assembly, vesicle size, and packaging of cargo molecules into COPII vesicles that we have tested but induces accumulation of procollagen in the endoplasmic reticulum when expressed in normal fibroblasts. We observed that M702V SEC23A activates SAR1B GTPase more than wild-type SEC23A when SEC13-SEC31 is present, indicating that M702V SEC23A causes premature dissociation of COPII from the membrane. Our results indicate that a longer stay of COPII proteins on the membrane is required to cargo procollagen than other molecules and suggest that the SEC23-SEC31 interface plays a critical role in capturing various cargo molecules.
Section of Genetics, Department of Pediatrics, University of California Davis Medical Center, Sacramento, California 95817.
Sun-Don
SD
Kim
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California Berkeley, Berkeley, California 94720, and.
Kanika Bajaj
KB
Pahuja
Department of Cell Physiology and Metabolism, University of Geneva Medical Center, 1211 Geneva 4, Switzerland.
Mariella
M
Ravazzola
Section of Genetics, Department of Pediatrics, University of California Davis Medical Center, Sacramento, California 95817.
Joonsik
J
Yoon
Section of Genetics, Department of Pediatrics, University of California Davis Medical Center, Sacramento, California 95817.
Simeon A
SA
Boyadjiev
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California Berkeley, Berkeley, California 94720, and.
Susan
S
Hammamoto
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California Berkeley, Berkeley, California 94720, and.
Randy
R
Schekman
Department of Cell Physiology and Metabolism, University of Geneva Medical Center, 1211 Geneva 4, Switzerland.
Lelio
L
Orci
Section of Genetics, Department of Pediatrics, University of California Davis Medical Center, Sacramento, California 95817,. Electronic address: jinoh.kim@ucdmc.ucdavis.edu.
Jinoh
J
Kim
D019943:Amino Acid Substitution; D000818:Animals; D022181:COP-Coated Vesicles / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020125:Mutation, Missense; D011347:Procollagen / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
D011347:Procollagen; D033921:Vesicular Transport Proteins