Question

A experimental drug XYZ blocks transport of proteins from the ER to the Golgi (anterograde transport), but not Golgi-to-ER trafficking (retrograde transport). Propose 3 possible targets of this drug

Answer 1

Membrane traffic between the endoplasmic reticulum and the golgi body is a carefully regulated process which is controlled by distinct anterograde (that is transport of proteins towards golgi) and retrograde (transport of proteins towards endoplasmic reticulum ) pathways. These two pathways link these two organelles which has different morphologies, structures, and localizations within the cell. ER is involved in multiple cellular functions ,protein biosynthesis ,folding, extends to the cell periphery,forms a dynamic tubule reticulum. On the other hand, golgi apparatus, does membrane sorting and recycling activities.

In order to block the anterograde pathway , a drug need to have linkage to these three activities:

A common regulatory system involving membrane assembly and disassembly is shared by these two pathway. A group of cytosolic coatomer proteins or golgi coat promoter proteins are involved in it. However if the drug help in creating certain conditions like BFA or Brefeldin A which prevents association of COP-I coat to the Golgi membrane thus preventing coatomer binding, then it can inhibit anterograde transport.

Also if the drug can act against conventional kinesin-dependent fast axonal transport which is required for anterograde pathway then it may perform this task.

If the drug has inhibitory effects on microtubule consisting of recombinant kinesin (kinesin-1) , then this drug can block anterograde pathway.