title: A positive signal prevents secretory membrane cargo from recycling between the Golgi and the ER.
abstract: The Golgi complex and ER are dynamically connected by anterograde and retrograde trafficking pathways. To what extent and by what mechanism outward-bound cargo proteins escape retrograde trafficking has been poorly investigated. Here, we analysed the behaviour of several membrane proteins at the ER/Golgi interface in live cells. When Golgi-to-plasma membrane transport was blocked, vesicular stomatitis virus glycoprotein (VSVG), which bears an ER export signal, accumulated in the Golgi, whereas an export signal-deleted version of VSVG attained a steady state determined by the balance of retrograde and anterograde traffic. A similar behaviour was displayed by EGF receptor and by a model tail-anchored protein, whose retrograde traffic was slowed by addition of VSVG's export signal. Retrograde trafficking was energy- and Rab6-dependent, and Rab6 inhibition accelerated signal-deleted VSVG's transport to the cell surface. Our results extend the dynamic bi-directional relationship between the Golgi and ER to include surface-directed proteins, uncover an unanticipated role for export signals at the Golgi complex, and identify recycling as a novel factor that regulates cargo transport out of the early secretory pathway.
authors: BIOMETRA Department, CNR Institute of Neuroscience, Università degli Studi di Milano, Milano, Italy.
authors: Matteo
authors: M
authors: Fossati
authors: BIOMETRA Department, CNR Institute of Neuroscience, Università degli Studi di Milano, Milano, Italy.
authors: Sara F
authors: SF
authors: Colombo
authors: BIOMETRA Department, CNR Institute of Neuroscience, Università degli Studi di Milano, Milano, Italy Department of Health Science, Magna Graecia University of Catanzaro, Catanzaro, Italy n.borgese@in.cnr.it.
authors: Nica
authors: N
authors: Borgese
mesh_terms: D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D021382:Protein Sorting Signals; D021381:Protein Transport; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D021382:Protein Sorting Signals; D014764:Viral Proteins
keywords: Rab6; VSV glycoprotein; live cell imaging; retrograde transport; secretory pathway