S. Lehtonen et al., In vivo interaction of the adapter protein CD2-associated protein with thetype 2 polycystic kidney disease protein, polycystin-2, J BIOL CHEM, 275(42), 2000, pp. 32888-32893
We identified a developmentally regulated gene from mouse kidney whose expr
ession is up-regulated in metanephrogenic mesenchyme cells when they are in
duced to differentiate to epithelial cells during kidney organogenesis. The
deduced 70.5-kDa protein, originally named METS-1 (mesenchyme-to-epitheliu
m transition protein with SH3 domains), has since been cloned as a CD2-asso
ciated protein (CD2AP). CD2AP is strongly expressed in glomerular podocytes
, and the absence of CD2AP in mice results in congenital nephrotic syndrome
. We have found that METS-1/CD2AP thereafter referred to as CD2AP) is expre
ssed at lower levels in renal tubular epithelial cells in the adult kidney,
particularly in distal nephron segments. Independent yeast two-hybrid scre
ens using the COOH-terminal region of either CD2AP or polycystin-2 as bait
identified the COOH termini of polycystin-2 and CD2AP, respectively, as str
ong interacting partners. This interaction was confirmed in cultured cells
by eo-immunoprecipitation of endogenous polycystin-2 with endogenous CD2AP
and vice versa. CD2AP shows a diffuse reticular cytoplasmic and perinuclear
pattern of distribution, similar to polycystin-2, in cultured cells, and t
he two proteins co-localize by indirect double immunofluorescence microscop
y. CD2AP is an adapter molecule that associates with a variety of membrane
proteins to organize the cytoskeleton around a polarized site. Such a funct
ion fits well with that hypothesized for the polycystin proteins in renal t
ubular epithelial cells, and the present findings suggest that CD2AP has a
role in polycystin-2 function.