A critical look at the function of the P2Y11 receptor

TY - JOUR

T1 - A critical look at the function of the P2Y11 receptor

AU - Dreisig, Karin

AU - Kornum, Birgitte Rahbek

PY - 2016/9/1

Y1 - 2016/9/1

N2 - The P2Y11 receptor is a member of the purinergic receptor family. It has been overlooked, somewhat due to the lack of a P2ry11 gene orthologue in the murine genome, which prevents the generation of knockout mice, which have been so helpful for defining the roles of other P2Y receptors. Furthermore, some of the studies reported to date have methodological shortcomings, making it difficult to determine the function of P2Y11 with certainty. In this review, we discuss the lack of a murine "P2Y11-like receptor" and highlight the limitations of the currently available methods used to investigate the P2Y11 receptor. These methods include protein recognition with antibodies that show very little specificity, gene expression studies that completely overlook the existence of a fusion transcript between the adjacent PPAN gene and P2RY11, and agonists/antagonists reported to be specific for the P2Y11 receptor but which have not been tested for activity on numerous other adenosine 5'-triphosphate (ATP)-binding receptors. We suggest a set of criteria for evaluating whether a dataset describes effects mediated by the P2Y11 receptor. Following these criteria, we conclude that the current evidence suggests a role for P2Y11 in immune activation with cell type-specific effects.

AB - The P2Y11 receptor is a member of the purinergic receptor family. It has been overlooked, somewhat due to the lack of a P2ry11 gene orthologue in the murine genome, which prevents the generation of knockout mice, which have been so helpful for defining the roles of other P2Y receptors. Furthermore, some of the studies reported to date have methodological shortcomings, making it difficult to determine the function of P2Y11 with certainty. In this review, we discuss the lack of a murine "P2Y11-like receptor" and highlight the limitations of the currently available methods used to investigate the P2Y11 receptor. These methods include protein recognition with antibodies that show very little specificity, gene expression studies that completely overlook the existence of a fusion transcript between the adjacent PPAN gene and P2RY11, and agonists/antagonists reported to be specific for the P2Y11 receptor but which have not been tested for activity on numerous other adenosine 5'-triphosphate (ATP)-binding receptors. We suggest a set of criteria for evaluating whether a dataset describes effects mediated by the P2Y11 receptor. Following these criteria, we conclude that the current evidence suggests a role for P2Y11 in immune activation with cell type-specific effects.

KW - Animals

KW - Humans

KW - Receptors

KW - Purinergic P2

U2 - 10.1007/s11302-016-9514-7

DO - 10.1007/s11302-016-9514-7

M3 - Review

C2 - 27246167

SN - 1573-9538

VL - 12

SP - 427

EP - 437

JO - Purinergic Signalling

JF - Purinergic Signalling

IS - 3

ER -