GRASP depletion–mediated Golgi destruction decreases cell adhesion and migration via the reduction of a5ß1 integrin

Ahat, Erpan; Xiang, Yi; Zhang, Xiaoyan; Bekier, Michael E.; Wang, Yanzhuang

Our results are consistent with previous reports that a higher expression level of α5 integrin or increased trafficking to the plasma membrane increases cell attachment and migration (Wan et al., 2014; Breuksch et al., 2017) . Given that the Golgi plays a critical role in protein glycosylation and sorting (Zhang and Wang, 2016; Huang and Wang, 2017) and that proper glycosylation of α5β1 integrin is important for its function and activation (Zheng et al., 1994; Guo et al., 2002; Gu and Taniguchi, 2004; Hang et al., 2017) , we expected that Golgi structural defects might affect integrin glycosylation, trafficking, and degradation. There are two possible reasons for the reduced α5β1-integrin level in GRASP-depleted cells: one is increased degradation, the other is decreased synthesis. Given that protein glycosylation has been thought to be a key mechanism to help protein folding and maintain protein stability (Live et al., 1996; Shental-Bechor and Levy, 2008; Sola and Griebenow, 2009; Lee et al., 2015) , we originally expected that GRASP depletion might affect integrin stability. However, the results demonstrated that GRASP depletion did not trigger integrin degradation by ERAD or its turnover; instead, it reduced α5β1-integrin synthesis, although the underlying mechanism remains unknown. In addition, GRASP depletion also accelerated α5-integrin trafficking and maturation, which is consistent with our previous findings (Xiang et al., 2013) .