PCDH7 Promotes Cell Migration by Regulating Myosin Activity

Abstract

Cell migration requires spatiotemporally coordinated activities of multicomponent structures including the actomyosin cortex, plasma membrane, adhesion complexes and the polarity proteins. How they function together to drive this complex dynamic process remains an outstanding question. Here, we show that a member of the protocadherin family, PCDH7 displays a polarized localization in migratory cells with a dynamic enrichment at the leading and rear edges. Perturbation of PCDH7 interferes with the migration of nontransformed retinal pigment epithelial cells and invasion of cancer cells. The overexpression of PCDH7 enhances the migration capability of cortical neurons in vivo. PCDH7 interacts with the myosin phosphatase subunits MYPT1 and PP1cβ and it enhances the phosphorylation of regulatory light chain and ERM at the leading and rear edges of migratory cells. The chemical inhibition of phosphatase activity recovers migration phenotypes of PCDH7 knockout cells. We propose that PCDH7 regulate phosphorylation thus activity of myosin and ERM at the polarized cortex by quenching myosin phosphatase that results in a higher persistence of migrating cells. Collectively, our study suggests a new mechanism for the spatial coordination of plasma membrane and the cortex during cell migration.

ZDHHC5 targets Protocadherin 7 to the cell surface by a palmitoylation-dependent mechanism to promote successful cytokinesis

“…Previously it was reported that PCDH7 increases phospho-myosin light chain levels to enhance anchorageindependent cell growth (Wang et al, 2020). Similarly, in a parallel study, we observed that PCDH7 overexpression enhances phospho-myosin levels during cell migration in Retinal Pigment Epithelial (RPE) cells and PCDH7 interacts with PP1cβ, the catalytic subunit, and MYPT1, the myosin targeting subunit of myosin phosphatase holoenzyme (Qureshi et al, 2021). Previous studies also reported that PCDH7 behaves as a signaling molecule more than an adhesion molecule and inhibits phosphatase activities of PP1a and PP2A (Wang et al, 2020;Zhou et al, 2017).…”

Single-Cell Analyses Offer Insights into the Different Remodeling Programs of Arteries and Veins

“…Of note, the over-representation of responses to me- Modulated SMCs express SMC genes, such as CNN1, and ITGA8, but show significant upregulation of "synthetic" markers like MYH10, FN1, and COL8A1 (Figure 5B, Data Set S1). Proinflammatory adhesion molecules (ALCAM) [53], promigratory mediators (PCDH7) [54], and modulation regulators (SPINT2) [55] are also upregulated in this subcluster. High levels of MYH10, FN1, COL8A1, and POSTN are also defining features of activated fibroblasts, along with significant upregulation of the thrombin receptor F2R, and the integrin ITGA10 (shared by arterial modulated SMCs).…”