Blockade of cadherin-6B activity perturbs the distribution of PSD-95 family proteins in retinal neurones

Background: Synaptic junctions have cadherin-catenin complexes, but their f unctions are poorly understood. Using retinal neurones, we investigated the role of this adhesion machinery in synaptic organization. Results: In cultures of chicken retinal cells, cadherin-6B (cad6B) and cadh erin-7 (cad7) are expressed by distinct neurones, each being distributed in a punctate pattern along their neurites as well as in the soma. Double-imm unostaining for cad6B and PSD-95/SAP90 or other PSD-95 family members, know n to localize in the postsynaptic density, showed that their distributions overlapped each other. To assess the role for cad6B, we incubated retinal c ells with antibodies that could specifically block cad6B-mediated adhesion. In the antibody-treated neurones, the localization pattern of PSD-95 famil y proteins was altered, that is, their staining signals tended to be reduce d or disarranged. We then examined whether cadherins interacted molecularly with PSD-95: Cadherin immunoprecipitates from brain lysates did not contai n PSD-95; nevertheless, this protein was co-precipitated with alpha N- and beta-catenins. When PSD-95 proteins were ectopically expressed in epithelia l cells, some of these molecules were concentrated in cell-cell junctions, co-localizing with E-cadherin, and this junctional localization of PSD-95 w as abolished by blocking of E-cadherin activity. Conclusion: These results suggest that cadherins play a role in the subcell ular organization of postsynaptic density components through some, perhaps indirect, molecular interactions.