SEC24A

In P. falciparum, SEC24A (PF3D7_1361100) functions as a COPII cargo adaptor at transitional ER (tER) sites, where it concentrates in distinct foci closely apposed to cis-Golgi elements marked by PfGRASP and packages secretory cargo for export from the ER (PMID:18410493). Its cargo-adaptor role is established by its capacity to accumulate a model cargo protein at these foci in a manner dependent on an intact diacidic export motif, distinguishing it from PfSec12, which is distributed throughout the ER (PMID:18410493). SEC24A also partially associates with the artemisinin-resistance protein K13 at these sites, as shown by co-immunoprecipitation and intermediate-to-high colocalization by quantitative IFA that is unchanged by dihydroartemisinin treatment (PMID:32310999). Beyond its localization to tER, its cargo-adaptor activity, and its partial association with K13 (PMID:18410493, PMID:32310999), no further mechanistic detail has been characterized in the available corpus.

1. 2008 High

   Whether P. falciparum organizes ER export at discrete transitional ER sites and which factor selects cargo there was unknown; identifying SEC24A as a focally concentrated cargo adaptor established the molecular basis of COPII-dependent ER export in the parasite.

   Evidence Live fluorescence imaging of GFP-tagged proteins, brefeldin A treatment, and site-directed mutagenesis of a cargo diacidic export motif in P. falciparum

   PMID:18410493

   Open questions at the time

   • The full endogenous cargo repertoire captured by SEC24A is not defined
   • The composition of the COPII coat complex assembled with SEC24A at tER is not resolved
   • No structural model of SEC24A cargo-motif recognition is provided
2. 2020 Medium

   Whether SEC24A physically and spatially associates with the artemisinin-resistance protein K13 was unknown; demonstrating co-immunoprecipitation and partial colocalization placed K13 at ER exit sites in proximity to the COPII machinery.

   Evidence Co-immunoprecipitation with K13-specific monoclonal antibodies and quantitative IFA (PCC analysis) on a Sec24a-GFP parasite line, with and without dihydroartemisinin, in P. falciparum

   PMID:32310999

   Open questions at the time

   • Single Co-IP plus IFA from one lab; reciprocal pulldown and direct interaction not established
   • Whether the SEC24A–K13 association is direct or bridged by other proteins is unresolved
   • Functional consequence of the association for cargo transport or drug resistance is not defined

• The endogenous cargo set, coat-complex partners, and the functional and mechanistic significance of SEC24A's proximity to K13 remain unresolved.
• No identified physiological cargo beyond the diacidic-motif model substrate
• No direct interaction map of the parasite COPII coat around SEC24A
• No test of whether SEC24A is required for K13-associated function or artemisinin resistance