Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2015 (2015), Article ID 319454, 13 pages
http://dx.doi.org/10.1155/2015/319454
Research Article

Prohibitin: A Novel Molecular Player in KDEL Receptor Signalling

1Department of Cellular and Translational Pharmacology, Fondazione Mario Negri Sud, 66030 Santa Maria Imbaro, Italy
2Department of Cell Biology & Signalling, The FIRC Institute of Molecular Oncology (IFOM), 20139 Milan, Italy
3Proteomic Core Facility, Fondazione Mario Negri Sud, 66030 Santa Maria Imbaro, Italy
4Institute of Protein Biochemistry, National Research Council and Telethon Institute of Genetics and Medicine, 80131 Naples, Italy

Received 5 December 2014; Accepted 14 April 2015

Academic Editor: Christian Appenzeller-Herzog

Copyright © 2015 Monica Giannotta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The KDEL receptor (KDELR) is a seven-transmembrane-domain protein involved in retrograde transport of protein chaperones from the Golgi complex to the endoplasmic reticulum. Our recent findings have shown that the Golgi-localised KDELR acts as a functional G-protein-coupled receptor by binding to and activating Gs and Gq. These G proteins induce activation of PKA and Src and regulate retrograde and anterograde Golgi trafficking. Here we used an integrated coimmunoprecipitation and mass spectrometry approach to identify prohibitin-1 (PHB) as a KDELR interactor. PHB is a multifunctional protein that is involved in signal transduction, cell-cycle control, and stabilisation of mitochondrial proteins. We provide evidence that depletion of PHB induces intense membrane-trafficking activity at the ER–Golgi interface, as revealed by formation of GM130-positive Golgi tubules, and recruitment of p115, β-COP, and GBF1 to the Golgi complex. There is also massive recruitment of SEC31 to endoplasmic-reticulum exit sites. Furthermore, absence of PHB decreases the levels of the Golgi-localised KDELR, thus preventing KDELR-dependent activation of Golgi-Src and inhibiting Golgi-to-plasma-membrane transport of VSVG. We propose a model whereby in analogy to previous findings (e.g., the RAS-RAF signalling pathway), PHB can act as a signalling scaffold protein to assist in KDELR-dependent Src activation.