Small molecule inhibition of intracellular transport
The present disclosure characterizes the activity of Golgicide A (GCA), as a potent, specific and reversible small molecule inhibitor of Golgi BFA resistance factor 1 (GBF1) function. A mutant GBF1 gene that is resistant to GCA is also described. Methods of using GCA and the GCA-resistant GBF1 gene are described including methods for modulating GBF1 activity for research and therapeutic purposes. Also described are compositions incorporating a GCA-resistant GBF1.
1. A method of inhibiting Golgi BFA resistance factor (GBF1) in a eukaryotic cell, the method comprising contacting the cell with Golgicide A.
2. The method of claim 1 , wherein contacting the cell with Golgicide A comprises contacting the cell with a solution of Golgicide A in an organic solvent.
3. The method of claim 2 , wherein the organic solvent is DMSO.
4. The method of claim 2 , wherein the solution of Golgicide A comprises Golgicide A at a concentration of from about 0.1 μM to about 100 μM.
5. The method of claim 4 , wherein the solution of Golgicide A comprises Golgicide A at a concentration of from about 5 μM to about 20 μM.
6. The method of claim 1 , wherein the eukaryotic cell is a mammalian cell.
7. The method of claim 1 , wherein the eukaryotic cell is a human cell.
8. The method of claim 1 , further comprising exposing the cell to a cytotoxin selected from the group consisting of: shiga toxin, cholera toxin, heat labile toxin, heat stable toxin, abrin, and ricin.
9. The method of claim 1 , further comprising at least partially reversing the effect of Golgicide A on GBF1 by wash-out of Golgicide A with a cell medium lacking Golgicide A.