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Chunk #9 — Results — CNIH-2 promotes ER export of GluAs

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AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.
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Cornichon and its orthologues have previously been described as cargo transporters, exporting soluble growth factors of the epidermal growth factor (EGF) family from the ER [25]–[27]. Based on our finding that exogenously expressed CNIH-2 cycles between ER and Golgi, we next addressed the question whether CNIH-2 might also serve as an ER cargo exporter for AMPA receptors. For this purpose, we used a heterologous expression system as the molecular mechanisms of selective ER export are conserved in all eukaryotic cells from yeast to mammalian cells including neurons [32]–[35]. Moreover, heterologous cells can be transfected at much higher rates than neurons allowing us to manipulate ER export of proteins and consecutively quantify their average surface expression in a representative number of cells. In opossum kidney (OK) cells stably expressing CNIH-2, ER export was blocked by transfection with a dominant-negative mutant of the small Ras-like GTPase Sar1 (Sar1 H79G) [36]. This constitutively active mutant of Sar1 prevents un-coating of transport vesicles, blocking ER export by inhibiting recycling of COPII components [37]. In OK cells expressing mutant Sar1 H79G, CNIH-2 was retained in