EHD2 expression is required for the presence of caveolae at the plasma membrane of breast cancer cells. (A–I) Survey view of the cytoplasmic surface of the plasma membrane in unroofed Hs578T cells (A–C), MDA-MB-436 (D–F) cells, and MDA-MB-436 cells transfected by EHD2-EGFP (G–I). For second inset (C, F, H, and I) use view glasses for 3D viewing of anaglyphs (left eye = red). Arrows indicate caveolae. Arrowheads indicate clathrin-coated pits. (J) Representative immunogold labeling of EM images of Cav1 protein localization in Hs578T and MDA-MB-436 cells. Scale bar = 200 nm. (K) Upon mechanical stress, Cav1, cavin1, and EHD2 are released from flattened caveolae. EHD2, but not cavin1 or Cav1, is SUMOylated and translocated to the nucleus where it controls gene transcription through interaction with MOKA and KLF-7. Upon stress release, EHD2 exits from the nucleus and is required for the stabilization of the caveolae reservoir at the plasma membrane.