A cycling cis-Golgi protein mediates endosome-to-Golgi traffic.
Toxins can invade cells by using a direct endosome-to-Golgi endocytic pathway that bypasses late endosomes/prelysosomes. This is also a route used by endogenous proteins, including GPP130, which is an integral membrane protein retrieved via the bypass pathway from endosomes to its steady-state location in the cis-Golgi. An RNA interference-based test revealed that GPP130 was required for efficient exit of Shiga toxin B-fragment from endosomes en route to the Golgi apparatus. Furthermore, two proteins whose Golgi targeting depends on endosome-to-Golgi retrieval in the bypass pathway accumulated in early/recycling endosomes in the absence of GPP130. GPP130 activity seemed specific to bypass pathway trafficking because the targeting of other tested proteins, including those retrieved to the Golgi via the more conventional late endosome route, was unaltered. Thus, a distally cycling Golgi protein mediates exit from endosomes and thereby underlies Shiga toxin invasion and retrieval-based targeting of other cycling Golgi proteins.
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Rajalaxmi
R
Natarajan
Adam D
AD
Linstedt
D001692:Biological Transport; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010750:Phosphoproteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D022621:Shiga Toxin / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D033921:Vesicular Transport Proteins
C107340:GOLIM4 protein, human; C410824:GOLM1 protein, human; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C072237:TGOLN2 protein, human; D033921:Vesicular Transport Proteins; D022621:Shiga Toxin