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 functions 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 cadherin-7 (cad7) are expressed by distinct neurones, each being distributed in a punctate pattern along their neurites as well as in the soma. Double-immunostaining for cad6B and PSD-95/SAP90 or other PSD-95 family members, known to localize in the postsynaptic density, showed that their distributions overlapped each other. To assess the role for cad6B, we incubated retinal cells with antibodies that could specifically block cad6B-mediated adhesion. In the antibody-treated neurones, the localization pattern of PSD-95 family proteins was altered, that is, their staining signals tended to be reduced or disarranged. We then examined whether cadherins interacted molecularly with PSD-95: Cadherin immunoprecipitates from brain lysates did not contain PSD-95; nevertheless, this protein was co-precipitated with alphaN- and beta-catenins. When PSD-95 proteins were ectopically expressed in epithelial cells, some of these molecules were concentrated in cell-cell junctions, co-localizing with E-cadherin, and this junctional localization of PSD-95 was abolished by blocking of E-cadherin activity.

Conclusion: These results suggest that cadherins play a role in the subcellular organization of postsynaptic density components through some, perhaps indirect, molecular interactions.