Protein sorting from endosomes to the TGN

Abstract

Retrograde transport from endosomes to the trans-Golgi network is essential for recycling of protein and lipid cargoes to counterbalance anterograde membrane traffic. Protein cargo subjected to retrograde traffic include lysosomal acid-hydrolase receptors, SNARE proteins, processing enzymes, nutrient transporters, a variety of other transmembrane proteins, and some extracellular non-host proteins such as viral, plant, and bacterial toxins. Efficient delivery of these protein cargo molecules depends on sorting machineries selectively recognizing and concentrating them for their directed retrograde transport from endosomal compartments. In this review, we outline the different retrograde transport pathways governed by various sorting machineries involved in endosome-to-TGN transport. In addition, we discuss how this transport route can be analyzed experimentally.

ER-export and ARFRP1/AP-1-dependent delivery of SARS-CoV-2 Envelope to lysosomes controls late stages of viral replication

“…ARFRP1 is needed for both the recruitment of golgins and GARP to the TGN 44 and controlling export of the planar cell polarity protein, Vangl2 45 . We show here that ARFRP1 is a TGN-localised GTPase whose GTPase activity is necessary for both AP-1 recruitment to the Golgi and for Golgi-to-endosome trafficking of E. AP-1 plays a complex role in bi-directional traffic between the Golgi and endosomes, acting alone in the retrograde pathway from endosomes-to-Golgi, and in-concert with GGAs and AP1AR/Gadkin in the anterograde pathway from Golgi-to-endosomes 28 . Consistent with role AP-1 in the anterograde movement of E, when this pathway was inactivated, we observed a failure of Golgi export, rather than a redistribution of E to endosomes.…”

“…Alternatively, the heterotetrameric clathrin adaptor complex AP-1 can select cargo for trans-Golgi Network (TGN)-to-endosome transport, where it works in-concert with the Golgi-localised Gamma-earcontaining Adaptor-1 (GGA1) and AP1AR/Gadkin, a kinesin adaptor responsible for the anterograde movement of AP-1 carriers [25][26][27] . An AP-3 dependent pathway is also thought to deliver cargo directly from Golgi to lysosomes, although this is less well characterised in mammalian cells 28 . Expression of a dominant negative form of the endocytic GTPase, Dynamin 29 , robustly blocked transferrin internalisation but had no impact on the intracellular 6 distribution of E-mEmerald (Fig.…”

ER-export and ARFRP1/AP-1–dependent delivery of SARS-CoV-2 Envelope to lysosomes controls late stages of viral replication

“…ARFRP1 is needed for both the recruitment of golgins and the Golgi Associated Retrograde Protein (GARP) complex to the TGN ( 51 ), binds AP-1 in a GTP-dependent manner, and controls TGN export of the planar cell polarity protein, Vangl2 ( 37 , 52 ). We show here that ARFRP1’s GTPase activity is necessary for both AP-1 recruitment to the Golgi and Golgi-to-endosome trafficking of E. AP-1 plays a complex role in bidirectional traffic between the Golgi and endosomes, acting alone in the retrograde pathway from endosomes to Golgi, and in concert with GGAs and AP1AR/Gadkin in the anterograde pathway from Golgi to endosomes ( 33 ). Consistent with the role of AP-1 in the anterograde movement of E, when this pathway was inactivated, we observed a failure of Golgi export, rather than a redistribution of E to endosomes.…”

“…Alternatively, the heterotetrameric clathrin adaptor complex, AP-1, can select cargo for TGN-to-endosome transport, where it works in concert with the Golgi-localized Gamma ear-containing adaptor-1 (GGA1) and AP1AR/Gadkin, a kinesin adaptor responsible for the anterograde movement of AP-1 carriers (30)(31)(32). An AP-3-dependent pathway is also thought to deliver cargo directly from Golgi to lysosomes, although this is less well characterized in mammalian cells (33). Expression of a dominant negative form of the endocytic GTPase, Dynamin (34), robustly blocked transferrin internalization but had no impact on the intracellular distribution of E-mEmerald (fig.…”

Deficiency of AP1 Complex Ap1g1 in Zebrafish Model Led to Perturbation of Neurodevelopment, Female and Male Fertility; New Insight to Understand Adaptinopathies

“…This is the reason for the higher rate of early to late endosome maturation and protein transport in pre-synapses of σ1B knockout mice. The σ1B encoding gene AP1S2 is encoded on the X-chromosome in mice and man and its deficiency causes severe X-linked intellectual disability and impaired motor coordination [ 6 ].…”