Ins and outs of GPCR signaling in primary cilia

TY - JOUR

T1 - Ins and outs of GPCR signaling in primary cilia

AU - Schou, Kenneth Bødtker

AU - Pedersen, Lotte Bang

AU - Christensen, Søren Tvorup

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Primary cilia are specialized microtubule-based signaling organelles that convey extracellular signals into a cellular response in most vertebrate cell types. The physiological significance of primary cilia is underscored by the fact that defects in assembly or function of these organelles lead to a range of severe diseases and developmental disorders. In most cell types of the human body, signaling by primary cilia involves different G protein-coupled receptors (GPCRs), which transmit specific signals to the cell through G proteins to regulate diverse cellular and physiological events. Here, we provide an overview of GPCR signaling in primary cilia, with main focus on the rhodopsin-like (class A) and the smoothened/frizzled (class F) GPCRs. We describe how such receptors dynamically traffic into and out of the ciliary compartment and how they interact with other classes of ciliary GPCRs, such as class B receptors, to control ciliary function and various physiological and behavioral processes. Finally, we discuss future avenues for developing GPCR-targeted drug strategies for the treatment of ciliopathies. GPCRs are involved in multiple signaling pathways in primary cilia. This article describes how GPCRs traffic into and out of the cilium and how they control ciliary and cellular functions. GPCR-targeted drug strategies for the treatment of ciliopathies are also discussed.

AB - Primary cilia are specialized microtubule-based signaling organelles that convey extracellular signals into a cellular response in most vertebrate cell types. The physiological significance of primary cilia is underscored by the fact that defects in assembly or function of these organelles lead to a range of severe diseases and developmental disorders. In most cell types of the human body, signaling by primary cilia involves different G protein-coupled receptors (GPCRs), which transmit specific signals to the cell through G proteins to regulate diverse cellular and physiological events. Here, we provide an overview of GPCR signaling in primary cilia, with main focus on the rhodopsin-like (class A) and the smoothened/frizzled (class F) GPCRs. We describe how such receptors dynamically traffic into and out of the ciliary compartment and how they interact with other classes of ciliary GPCRs, such as class B receptors, to control ciliary function and various physiological and behavioral processes. Finally, we discuss future avenues for developing GPCR-targeted drug strategies for the treatment of ciliopathies. GPCRs are involved in multiple signaling pathways in primary cilia. This article describes how GPCRs traffic into and out of the cilium and how they control ciliary and cellular functions. GPCR-targeted drug strategies for the treatment of ciliopathies are also discussed.

U2 - 10.15252/embr.201540530

DO - 10.15252/embr.201540530

M3 - Review

C2 - 26297609

SN - 1469-221X

VL - 16

SP - 1099

EP - 1113

JO - E M B O Reports

JF - E M B O Reports

IS - 9

ER -