Primary cilia regulates endothelial cell directional migration through HSP‐27 dependent modulation of actin cytoskeleton and focal adhesions

Abstract

Cilia are mechano/chemo‐sensing organelles that communicate extracellular mechanical signals to intracellular responses. Altered function of primary cilia plays a key role in the development of various diseases including polycystic kidney disease. Here, we show that endothelial cells from the oak ridge polycystic kidney (ORPK) mouse with impaired assembly of cilia, exhibits a reduced formation of actin stress fibers and focal adhesions compared to wild type endothelial cells. Further, these cells showed decreased directional migration in scratch‐wound assays. Interestingly, we found that expression of heat shock protein‐27 (hsp‐27), which is required for the organization of the actin cytoskeleton, is down regulated in these cells. However, the phosphorylation of focal adhesion kinase (FAK), a known downstream effector of hsp‐27, is unchanged. Taken together, these results demonstrate that disruption of primary cilia formation compromises endothelial cell directional migration through the suppression of hsp‐27 dependant F‐actin organization and focal adhesion formation which may lead to vascular dysfunction in ciliopathies.