Several lines of evidence indicate that a family of Sec24 proteins functions in cargo recognition. Furthermore, the presence of multiple Sec24 homologues appears to expand the variety of cargo that must be efficiently exported from the ER. Yeast cells express two additional Sec24-like proteins: Lst1 and Iss1, and higher eukaryotes are endowed with at least four Sec24 isoforms (Pagano et al. 1999, and see above). In yeast, the Lst1 subunit is not essential for COPII-dependent export but is required for efficient export of specific transmembrane cargos from the ER (Roberg et al. 1999; Shimoni et al. 2000). Both Sec23-Sec24 and Sec23-Lst1 proteins can be incorporated into a continuous COPII structure, suggesting that heterogeneity in the coat could increase the variety of cargo accommodated by a COPII-coated vesicle (Shimoni et al. 2000). In a functional sorting assay it was shown that both Sec23-Sec24 and Sec23-Lst1 can function independently in assembly of COPII coats; however, the spectrum of cargo packaged into vesicles synthesized with Sec23-Sec24 was quite distinct from those generated with Sec23-Lst1 (Miller et al. 2002). These observations, coupled with the fact that Sec23-Sec24 displays binding affinities for both di-acidic (Vostmeier and Gallwitz 2001) and di-hydrophobic motifs (Kappeler et al. 1997; Dominguez et al. 1998; Belden and Barlowe 2001), support a direct role for Sec24 in cargo recognition. Sec24p has indeed been shown to contain multiple cargo binding sites to ensure capture of diverse membrane proteins into transport vesicles (Miller et al. 2003).
Although plant cells also contain several Sec24 isoforms, there is no information on the binding specificity of Sec24 towards different ER export signals. Alternatively, Sar1 may also contribute to cargo recognition through direct association with export signals to form stable prebudding complexes. In this respect, Sar1p has also been shown to interact with export cargo, including VSV-G (Aridor et al. 1998), the v-SNAREs Bos1p and Bet1p (Springer and Schekman 1998), p24 proteins (Belden and Barlowe 2001) and the Erv41p/Erv46p complex (Otte and Barlowe 2002). In the case of glycosyltrans-ferases, binding to Sar1p specifically involves di-basic motifs (Giraudo and Maccioni 2003).
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