Sec24 proteins and sorting at the endoplasmic reticulum

COPII proteins are necessary to generate secretory vesicles at the endoplas mic reticulum, In yeast, the Sec24p protein is the only COPII component in which two close orthologues have been identified. By using gene knock-out i n yeast, we found that the absence of one of these Sec24 orthologues result ed in a selective secretion defect for a subset of proteins released into t he medium. Data base searches revealed the existence of an entire family of Sec24-related proteins in humans, worms, flies, and plants. We identified and cloned two new human cDNAs encoding proteins homologous to yeast Sec24p , in addition to two human cDNAs already present within the data bases. The entire Sec24 family identified to date is characterized by clusters of hig hly conserved residues within the 2/3 carboxyl-terminal domain of all the p roteins and a divergent amino terminus domain. Human (h) Sec24 orthologues co-immunoprecipitate with hSec23Ap and migrate as a complex by size exclusi on chromatography. Immunofluorescence microscopy confirmed that these prote ins co-localize with hSec23p and hSec13p. Together, our data suggest that i n addition to its role in the shaping up of the vesicle, the Sec23-24p comp lex may be implicated in cargo selection and concentration.