PAQR3 regulates Golgi vesicle fission and transport via the Gβγ-PKD signaling pathway

Cellular Signalling
Thamara Hewavitharana, Philip B Wedegaertner

Abstract

Heterotrimeric G proteins function at diverse subcellular locations, in addition to canonical signaling at the plasma membrane (PM). Gβγ signals at the Golgi, via protein kinase D (PKD), to regulate fission of PM-destined vesicles. However, the mechanism by which Gβγ is regulated at the Golgi in this process remains elusive. Recent studies have revealed that PAQR3 (Progestin and AdipoQ Receptor 3), also called RKTG (Raf Kinase Trapping to the Golgi), interacts with the Gβ subunit and localizes Gβ to the Golgi thereby inhibiting Gβγ signaling at the PM. Herein we show that, in contrast to this inhibition of canonical Gβγ signaling at the PM, PAQR3 promotes Gβγ signaling at the Golgi. Expression of PAQR3 causes fragmentation of the Golgi, while a Gβ binding-deficient mutant of PAQR3 does not cause Golgi fragmentation. Also, a C-terminal fragment of GRK2 (GRK2ct), which interacts with Gβγ and inhibits Gβγ signaling, and gallein, a small molecule inhibitor of Gβγ, are both able to inhibit PAQR3-mediated Golgi fragmentation. Furthermore, a dominant negative form of PKD (PKD-DN) and a pharmacological inhibitor of PKD, Gö6976, also inhibit PAQR3-mediated fragmentation of the Golgi. Importantly, expression of the Gβ binding-deficient m...Continue Reading

References

Aug 9, 1996·Science·N B ColeJ Lippincott-Schwartz
Apr 22, 2006·Science·Tabetha M BonacciAlan V Smrcka
Nov 28, 2006·Frontiers in Bioscience : a Journal and Virtual Library·Alberto AnelMaria Jose Martinez-Lorenzo
Jun 15, 2007·Biochemistry·Yannick MarrariPhilip B Wedegaertner
Mar 26, 2008·Biochemistry·Yixing ZhouT Kendall Harden
Oct 12, 2010·Cold Spring Harbor Perspectives in Biology·Jane E Visvader, Gilbert H Smith
Mar 23, 2011·Cold Spring Harbor Perspectives in Biology·Vivek Malhotra, Felix Campelo

❮ Previous
Next ❯

Citations

Jul 6, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shahriar M KhanTerence E Hébert
Jun 10, 2021·Molecular Biology of the Cell·Mithila TennakoonAjith Karunarathne
Jul 15, 2021·Molecular Biology of the Cell·Kalpana RajanalaPhilip B Wedegaertner

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomegaly

Cardiomegaly, known as an enlarged heart, is a multifactorial disease with different pathophysiological mechanisms. Hypertension, pregnancy, exercise-induced and idiopathic causes are some mechanisms of cardiomegaly. Discover the latest research of cardiomegaly here.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.