Intercellular adhesion molecule-5 (ICAM-5) is a dendritically polarized mem
brane glycoprotein in telencephalic neurons, which shows heterophilic bindi
ng to leukocyte beta(2)-integrins. Here, we show that the human ICAM-5 prot
ein interacts in a hemophilic manner through the binding of the immunoglobu
lin domain 1 to domains 4-5. Surface coated ICAM-5-Fc promoted dendritic ou
tgrowth and arborization of ICAM-5-expressing hippocampal neurons. During d
endritogenesis in developing rat brain, ICAM-5 was in monomer form, whereas
in mature neurons it migrated as a high molecular weight complex. The find
ings indicate that its homophilic binding activity was regulated by nonmono
mer/monomer transition. Thus, ICAM-5 displays two types of adhesion activit
y, homophilic binding between neurons and heterophilic binding between neur
ons and leukocytes.