CKAP4 Regulates Cell Migration via the Interaction with and Recycling of Integrin.

ABSTRACT: Cytoskeleton-associated protein 4 (CKAP4) is an endoplasmic reticulum protein that is also present in the cell surface membrane, where it acts as a receptor for Dickkopf1 (DKK1). In this study, we found that CKAP4 interacts with ?1 integrin and controls the recycling of ?5?1 integrin independently of DKK1. In S2-CP8 cells, knockdown of CKAP4 but not DKK1 enlarged the size of cell adhesion sites and enhanced cell adhesion to fibronectin, resulting in decreased cell migration. When CKAP4 was depleted, the levels of ?5 but not ?1 integrin were increased in the cell surface membrane. A similar phenotype was observed in other cells expressing low levels of DKK1. In S2-CP8 cells, ?5 integrin was trafficked with ?1 integrin and CKAP4 to the lysosome or recycled with ?1 integrin. In CKAP4-depleted cells, the internalization of ?5?1 integrin was unchanged, but its recycling was upregulated. Knockdown of sorting nexin 17 (SNX17), a mediator of integrin recycling, abrogated the increased ?5 integrin levels caused by CKAP4 knockdown. CKAP4 bound to SNX17, and its knockdown enhanced the recruitment of ?5?1 integrin to SNX17. These results suggest that CKAP4 suppresses the recycling of ?5?1 integrin and coordinates cell adhesion sites and migration independently of DKK1.

SUBMITTER: Osugi Y 

PROVIDER: S-EPMC6664606 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature