TGN38 cycles via the basolateral membrane of polarized Caco-2 cells.
TGN38 is a heavily glycosylated, type I integral membrane protein which is predominantly localized to the trans Golgi network (TGN), but which constitutively traffics between the TGN and the cell surface. The trafficking of TGN38 has been extensively studied in non-polarized cells, and a short, tyrosine-based, peptide motif within the cytosolic domain of the protein has been shown to be necessary and sufficient for its rapid internalization from the cell surface and efficient delivery to the TGN. Such tyrosine-based motifs have also been shown to act as basolateral targeting signals, whilst N-linked glycans (as occur on the extracytosolic domain of TGN38) can act as apical targeting signals. TGN38 has previously been shown to be sorted to the basolateral surface of polarized canine MDCK cells; a polarized cell line in which biosynthetic sorting decisions concerning the eventual destination of apical or basolateral targeted plasma membrane proteins are made at the TGN. We now show that TGN38 is targeted exclusively to the basolateral domain of polarized human Caco-2 cells, a cell line in which newly synthesized membrane proteins destined for either the apical or basolateral plasma membrane may be sorted for delivery to their final destination either at the TGN or at the cell surface. These data also demonstrate that the heavily glycosylated, extracytosolic domain of TGN38 does not contain a dominant apical targeting signal.
Reaves
B J
BJ
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, UK.
Roquemore
E P
EP
Luzio
J P
JP
Banting
G
G
D000818:Animals; D001692:Biological Transport; D018938:Caco-2 Cells; D016764:Cell Polarity; D006023:Glycoproteins; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008565:Membrane Proteins; D051381:Rats
D006023:Glycoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C072237:TGOLN2 protein, human; C513045:Tgoln2 protein, rat