Mitotic ER exit site dissociation and reassembly is regulated by TANGO1 phosphorylation status

Abstract

1Golgi fragmentation and ER exit site dissociation are considered as the leading 2 causes of mitotic block of secretion from the ER. Although the mechanisms of Golgi 3 fragmentation have been extensively characterized, ER exit block early in mitosis is 4 not well-understood. We previously found that TANGO1 organizes ER exit sites by 5 directly interacting with Sec16. Here, we showed that TANGO1 is phosphorylated 6 by casein kinase 1 (CK1) during mitosis. Interestingly, the interaction with Sec16 7 was abrogated by phosphorylation of TANGO1, leading to dissociation of the ER 8 exit sites. Moreover, a TANGO1 mutant deficient in phosphorylation inhibited the 9 mitotic dissociation of ER exit sites. In contrast, a TANGO1 mutant mimicking 10 CK1-mediated phosphorylation dissociated ER exit sites in interphase cells. 11