Retrograde transport of cholera toxin from the plasma membrane to the endoplasmic reticulum requires the trans-Golgi network but not the Golgi apparatus in Exo2-treated cells.
Cholera toxin (CT) follows a glycolipid-dependent entry pathway from the plasma membrane through the trans-Golgi network (TGN) to the endoplasmic reticulum (ER) where it is retro-translocated into the cytosol to induce toxicity. Whether access to the Golgi apparatus is necessary for transport to the ER is not known. Exo2 is a small chemical that rapidly blocks anterograde traffic from the ER to the Golgi and selectively disrupts the Golgi apparatus but not the TGN. Here we use Exo2 to determine the role of the Golgi apparatus in CT trafficking. We find that under the condition of complete Golgi ablation by Exo2, CT reaches the TGN and moves efficiently into the ER without loss in toxicity. We propose that even in the absence of Exo2 the glycolipid pathway that carries the toxin from plasma membrane into the ER bypasses the Golgi apparatus entirely.
Feng
Yan
Y
Department of Cell Biology, Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jadhav
Ashutosh P
AP
Rodighiero
Chiara
C
Fujinaga
Yukako
Y
Kirchhausen
Tomas
T
Lencer
Wayne I
WI
D000818:Animals; D001547:Benzaldehydes / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002772:Cholera Toxin / Q000032:analysis / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004553:Electric Conductivity; D004721:Endoplasmic Reticulum / Q000502:physiology*; D006023:Glycoproteins / Q000032:analysis; D006056:Golgi Apparatus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology*; D018000:Receptors, Peptide / Q000032:analysis; D021601:trans-Golgi Network / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*
C495416:4-hydroxy-3-methoxy-(5,6,7,8-tetrahydro(1)benzothieno(2,3-d)pyrimidin-4-yl)hydrazone benzaldehyde; D001547:Benzaldehydes; D006023:Glycoproteins; C064459:KDEL receptor; D011743:Pyrimidines; D018000:Receptors, Peptide; D005576:Colforsin; D002772:Cholera Toxin