GRE Subject Test: Biochemistry, Cell, and Molecular Biology › Help with Nuclear Transport
Which of the following choices would have the biggest effect on nuclear transport?
A mutated, non-functional copy of RanGAP
An inhibitor that globally targets importins at their cargo binding sites
An inhibitor that globally targets exportins at their cargo binding sites
A non-functional copy of the gene that encodes CRM1
Because the question is asking which will have the largest effect, it makes sense that the answer should affect import and export globally.
Importins and exportins only work in one direction. While mutations to either of these protein classes would greatly affect nuclear transport, each is only responsible for "half" or the transport across the membrane. CRM1 is a well characterized exportin.
RanGAP, however, is responsible for helping maintain the gradient of Ran bound to GTP or GDP. The gradient of RanGTP/GDP is what provides global directionality to nuclear import and export. Loss of RanGAP would affect both import and export, having the largest detrimental effect on nuclear transport.
What is the function of RanGAP in relation to nuclear import and export?
Maintain a gradient of GTP/GDP bound Ran
Bind cargo proteins
Bind importins/exportins and bring them through the nuclear pore complex
Attach GTP to Ran
RanGAP is notable for its ability to activate the GTPase function of the Ran protein. This allows for the hydrolysis of the third phosphate of GTP-bound Ran and the maintenance of a Ran-GDP/Ran-GTP gradient that is used to control nuclear import and export. RanGAP does not directly associate with cargo proteins or importins/exportins.