Alanine-(87)-threonine polymorphism impairs signaling and internalization of the human P2Y11 receptor, when co-expressed with the P2Y1 receptor.

The human P2Y(11) nucleotide receptor plays key role in immune-responses in brain and other tissues. We provide evidence for significant functional disturbance of the P2Y(11) receptor carrying the Alanine-87-Threonine mutation caused by natural polymorphism. This receptor defect is apparent only when co-expressed with P2Y(1) receptors. We found reductions in ligand-induced calcium and cAMP responses and in nucleotide-induced receptor internalization / resensitization. Thus, prolonged nucleotide treatments are the basis for the molecular defects of the mutant receptor in diseases.