Dephosphorylation of CCTbeta is required for the efficient secretory cargo export from the endoplasmic reticulum

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Phosphocholine cytidylyltransferase (CCT), the rate-limiting enzyme in the CDP-choline pathway for phosphatidylcholine (PC) synthesis, is activated by its translocation to membranes for efficient PC production. CCTbeta is translocated onto the ER membranes upon oleate addition. We found that knockdown of CCTbeta caused slowed export of secretory cargo. To understand the mechanism, we studied the oleate-induced translocation and then the CCTbeta was dephosphorylated in the membranes. We identified PP2Cepsilon as the protein responsible for the dephosphorylation of CCTbeta. Detailed analysis showed that exchange of Sec13 of the ERES with the cytoplasmic pool was markedly inhibited by knockdown of either CCTbeta or PP2Cepsilon to similar extent while the diffusibility of Sec13 in the cytoplasm remained unchanged. We propose that dephosphorylation of CCTbeta directly regulates COPII-mediated export of secretary cargo.