Dataset Information

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

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

Osugi Yoshihito Y Fumoto Katsumi K Kikuchi Akira A

Molecular and cellular biology 20190729 16

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 β1 integrin and controls the recycling of α5β1 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 deple ...[more]

PMID: 31160493

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Project description:Adhesive and migratory behavior can be cell type, integrin, and substrate dependent. We have compared integrin and substrate differences using three integrin receptors: ?5?1, ?6?1, and ?L?2 expressed in a common cell type, CHO.B2 cells, which lack integrin ? subunits, as well as in different cell types that express one or more of these integrins. We find that CHO.B2 cells expressing either ?6?1 or ?L?2 integrins migrate and protrude faster and are more directionally persistent on laminin or ICAM-1, respectively, than CHO.B2 cells expressing ?5?1 on fibronectin. Despite rapid adhesion maturation and the presence of large adhesions in both the ?6?1- and ?L?2-expressing cells, they display robust tyrosine phosphorylation. In addition, whereas myosin II regulates adhesion maturation and turnover, protrusion rates, and polarity in cells migrating on fibronectin, surprisingly, it does not have comparable effects in cells expressing ?6?1 or ?L?2. This apparent difference in the integration of myosin II activity, adhesion, and migration arises from alterations in the ligand-integrin-actin linkage (molecular clutch). The elongated adhesions in the protrusions of the ?6?1-expressing cells on laminin or the ?L?2-expressing cells on ICAM-1 display a novel, rapid retrograde flux of integrin; this was largely absent in the large adhesions in protrusions of ?5?1-expressing cells on fibronectin. Furthermore, the force these adhesions exert on the substrate in protrusive regions is reduced compared to similar regions in ?5-expressing cells, and the adhesion strength is reduced. This suggests that intracellular forces are not efficiently transferred from actomyosin to the substratum due to altered adhesion strength, that is, avidity, affinity, or the ligand-integrin-actin interaction. Finally, we show that the migration of fast migrating leukocytes on fibronectin or ICAM-1 is also largely independent of myosin II; however, their adhesions are small and do not show retrograde fluxing suggesting other intrinsic factors determine their migration differences.

Dataset Information

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

Publications

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

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