Selective regulation of the Rab9-independent transport of ricin to the Golgi apparatus by calcium.
Transport of ricin from endosomes to the Golgi apparatus occurs, in contrast to the transport of the mannose 6-phosphate receptor, by a Rab9-independent process. To characterize the pathway of ricin transport to the Golgi apparatus, we investigated whether it was regulated by calcium. As shown here, our data indicate that calcium is selectively involved in the regulation of ricin transport to the Golgi apparatus. Thapsigargin, which inhibits calcium transport into the ER, and the calcium ionophore A23187 both increased the transport of ricin to the Golgi apparatus by a factor of 20. By contrast, transport of the mannose 6-phosphate receptor to the Golgi apparatus was unaffected. Ricin and mannose 6-phosphate receptor transport were measured by quantifying the sulfation of modified forms of ricin and the mannose 6-phosphate receptor. The increased transport of ricin was reduced by wortmannin and LY294002, suggesting that phosphoinositide 3-kinase might be involved in transport of ricin to the Golgi apparatus. Together, these findings indicate that the different pathways to the Golgi apparatus utilized by ricin and the mannose 6-phosphate receptor are regulated by different mechanisms.
Lauvrak
Silje U
SU
Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway.
Llorente
Alicia
A
Iversen
Tore-Geir
TG
Sandvig
Kirsten
K
D000730:Androstadienes / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D016764:Cell Polarity; D002867:Chromones / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D004791:Enzyme Inhibitors / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D007476:Ionophores / Q000378:metabolism; D009025:Morpholines / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D021381:Protein Transport; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D012276:Ricin / Q000378:metabolism*; D022621:Shiga Toxin / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D019284:Thapsigargin / Q000378:metabolism; D000077191:Wortmannin; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D000730:Androstadienes; D000001:Calcimycin; D002118:Calcium; D002867:Chromones; D004791:Enzyme Inhibitors; D007476:Ionophores; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017527:Receptor, IGF Type 2; D012276:Ricin; D022621:Shiga Toxin; D013431:Sulfates; D019284:Thapsigargin; D000077191:Wortmannin; D020691:rab GTP-Binding Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C079856:RAB9A protein, human