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

磷脂酰胆碱胞苷酰转移酶（CCT）是CDP-胆碱途径中磷脂酰胆碱（PC）合成的限速酶，通过转运至细胞膜而被激活，以有效生产PC。加入油酸盐后，CCT β易位到ER膜上。我们发现，敲低CCT β导致分泌货物的出口放缓。为了理解其机制，我们研究了油酸诱导的易位，然后CCT β在膜中去磷酸化。我们鉴定出PP 2C β是负责CCT β去磷酸化的蛋白质。详细的分析表明，ERES的Sec 13与细胞质池的交换被敲低CCT β或PP 2C β至相似程度的显著抑制，而Sec 13在细胞质中的扩散性保持不变。我们认为，去磷酸化的CCT β直接调节COPII介导的出口的秘书货物。

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.