CONICET | Buscador de Institutos y Recursos Humanos

Clustered protocadherins (Pcdh) are surface glycoproteins expressed in specific regions of the central nervous system of vertebrates. Because of their similarity with other adhesion molecules and enriched presence at synapses, they could be involved in determining the specificity of some synaptic connections. They are encoded by three closely related gene clusters: alpha, beta, and gamma. Alternative splicing generates multiple alpha and gamma isoforms, potentially producing enormous variability in cell surface molecules. We are interested in understanding the biological role of this diversity and whether these proteins engage in homo or heterophylic interactions. We propose certain Pcdh isoforms have different roles from other members of the cluster. We have found evidence for this. When overexpressed, the alpha c2 isoform localizes to cell-to-cell contacts in a calcium-dependent manner, retrieving from the plasma membrane to vesicles when extracellular Ca2+ levels decrease, as opposed to other alpha isoforms tested. We are confirming these observations in stable cell lines. To test for protein interactions in a different way, we have expressed Pcdh extracellular domains using the baculovirus expression system, challenging cells expressing a certain isoform with the same or different soluble Pcdh. We hope our research helps to understand the nature of the interactions between Pcdh.