Protein transport from the secretory to the endocytic pathway in mammalian cells.
The trans-Golgi network (TGN) is the last station of the secretory pathway where soluble and membrane proteins are sorted for subsequent transport to endocytic compartments. This pathway is primarily followed by two distinct but related mannose 6-phosphate receptors which exhibit complementary functions in soluble lysosomal enzyme targeting. These transmembrane proteins and their bound ligands are packaged in transport intermediates coated with clathrin and the AP-1 assembly complex. Their segregation is determined by the interaction of tyrosine- and di-leucine-based sorting determinants present in their cytoplasmic domains with AP-1. Other membrane proteins such as the lysosomal membrane glycoproteins or envelope glycoproteins of herpes viruses, which contain similar sorting signals, may also follow the same pathway. In this review, we will summarize our current understanding of the molecular mechanisms leading to membrane protein sorting in the TGN and the formation of AP-1-coated transport intermediates.
Le Borgne
R
R
Institut de Biologie de Lille, EP CNRS 525, Institut Pasteur de Lille, BP 447, 1, rue Professeur Calmette, 59021 Lille Cédex, France.
Hoflack
B
B
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001692:Biological Transport; D003034:Coated Pits, Cell-Membrane; D003594:Cytoplasmic Granules / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D008322:Mammals; D008565:Membrane Proteins / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000502:physiology
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D008565:Membrane Proteins; D017527:Receptor, IGF Type 2