MURINE VASCULAR CELL-ADHESION MOLECULE-1 (VCAM-1) PROTEINS ENCODED BYALTERNATIVELY SPLICED MESSENGER-RNAS ARE DIFFERENTIALLY TARGETED IN POLARIZED CELLS

VCAM-1 is an immunoglobulin (Ig) superfamily member expressed in endot helial cells that mediates adhesion to a variety of leukocytes in a VL A-4 dependent manner. In the mouse, two distinct forms of VCAM are pro duced. One form, VCAM(TM), contains seven Ig domains followed by a sin gle transmembrane region and a short cytoplasmic domain. A second form , VCAM(GPI), which is preferentially induced by cytokines and LPS, con tains only the first three Ig domains and is attached to the cell surf ace via a glycosylphosphatidylinositol (GPI) anchor. Both vascular and nonvascular expression of VCAM have been reported in a variety of nor mal and pathological settings. One possible role for the two VCAM isof orms is to allow for the targeted localization of VCAM to specific cel l surface domains of polarized cells. This may be particularly relevan t since VCAM is known to be expressed by two different polarized cell types, namely endothelial cells and kidney epi thelial cells. In this study, MDCK cells permanently expressing either VCAM(TM) or VCAM(GPI) were established and used to examine the targeting of VCAM proteins to different polarized surface domains. VCAM(TM) was primarily located o n the basolateral surface while VCAM(GPI) was located on the apical su rface of polarized MDCK cells. Data is also presented that demonstrate s that polarized expression is reversed in endothelial cells where VCA M(TM) was observed primarily on the apical surface. The differential l ocalization of VCAM isoforms on the cell surface has direct implicatio ns for the ability of VCAM to mediate cell adhesion and transmigration .