Intracellular sorting and transport of proteins

Abstract

The secretory and endocytic pathways of eukaryotic organelles consist of multiple compartments, each with a unique set of proteins and lipids. Specific transport mechanisms are required to direct molecules to defined locations and to ensure that the identity, and hence function, of individual compartments are maintained. The localisation of proteins to specific membranes is complex and involves multiple interactions. The recent dramatic advances in understanding the molecular mechanisms of membrane transport has been due to the application of a multi-disciplinary approach, integrating membrane biology, genetics, imaging, protein and lipid biochemistry and structural biology. The aim of this review is to summarise the general principles of protein sorting in the secretory and endocytic pathways and to highlight the dynamic nature of these processes. The molecular mechanisms involved in this transport along the secretory and endocytic pathways are discussed along with the signals responsible for targeting proteins to different intracellular locations.

Ciliary Neurotrophic Factor Activates Astrocytes, Redistributes Their Glutamate Transporters GLAST and GLT-1 to Raft Microdomains, and Improves Glutamate HandlingIn Vivo

“…Removal of glycosylation sites on glutamate transporters does not directly affect transport properties but can reduce the stability of GLT-1 (Raunser et al, 2005), decrease the formation of the multimeric, active forms of GLAST (Conradt et al, 1995) or decrease the cell-surface expression of GLT-1 . Indeed, N-linked glycans play a pivotal role in protein sorting to subcellular compartments (van Vliet et al, 2003) and could be involved in protein targeting to raft domains (Simons and Ikonen, 1997;Fullekrug and Simons, 2004). We speculate that glutamate transporter redistribution into rafts could be mediated by a change in their pattern of glycosylation.…”

“…4). Because the pattern of protein glycosylation is a targeting signal (van Vliet et al, 2003), we wanted to assess whether the localization of the highly glycosylated transporters was altered. However, studying the subcellular localization of glutamate transporters using immunofluorescence is difficult to perform in vivo.…”

Bone Marrow Stromal Cell Antigen 2 Is a Specific Marker of Type I IFN-Producing Cells in the Naive Mouse, but a Promiscuous Cell Surface Antigen following IFN Stimulation

“…A function in sorting transmembrane and secreted proteins is further indicated by BST2 sequence and topology. BST2 shows sequence homology with BAP31, a chaperone involved in intracellular transport of cell surface proteins, and contains sequence motifs, such as an N terminus tyrosine-based motif (Y-x-Y-x-x-x-P-M, Y, tyrosine; P, proline; M, methionine; x, any amino acid) and KKxx (K, lysine; x, any amino acid) that may function as transport signals (30). Finally, BST2 presents an unusual topology with an N terminus transmembrane domain and a C terminus GPI anchor that locates BST2 in glycosphingolipids-and cholesterol-rich lipid microdomains (29).…”

Human RME-8 Is Involved in Membrane Trafficking through Early Endosomes

“…In addition, certain molecules are targeted to other compartments, such as the trans-Golgi network (TGN). These membrane trafficking events are controlled by many proteins including adaptor molecules, Rab GTPases and SNAREs (van Vliet et al, 2003).…”