ASSOCIATION OF EZRIN WITH INTERCELLULAR-ADHESION MOLECULE-1 AND MOLECULE-2 (ICAM-1 AND ICAM-2) - REGULATION BY PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE

Ezrin is a cytoplasmic linker molecule between plasma membrane compone nts and the actin-containing cytoskeleton. We studied whether ezrin is associated with intercellular adhesion molecule (ICAM)-1, 2, and -3. In transfected cells, ICAM-1 and ICAM-2 colocalized with ezrin in micr ovillar projections, whereas an ICAM-2 construct attached to cell memb rane via a glycophosphatidyl-inositol anchor was uniformly distributed on the cell surface. An interaction of ICAM-2 and ezrin was seen by a ffinity precipitation, microtiter binding assay, coimmunoprecipitation , and surface plasmon resonance methods. The calculated K-D, value was 3.3 x 10(-7) M. Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P-2 ) induced an interaction of ezrin and ICAM-1 and enhanced the interact ion of ezrin and ICAM-2, but ICAM-3 did not bind ezrin even in the pre sence of PtdIns(4,5)P-2. PtdIns(4,5)P-2 was shown to bind to cytoplasm ic tails of ICAM-1 and ICAM-2, which are the first adhesion proteins d emonstrated to interact with PtdIns(4,5)P-2. The results indicate an i nteraction of ezrin with ICAM-1 and ICAM-2 and suggest a regulatory ro le of phosphoinositide signaling pathways in regulation of ICAM-ezrin interaction.