Ran in Nucleocytoplasmic Transport - Ras Superfamily Small G Proteins: Biology and Mechanisms 2 - page 108

a karyopherin

cargo

nuclear
import
complex

Ran
GDP

cytoplasm

RanGA P

nucleus

Ran
GTP

Ran
GTP

cargo

b

cargo

karyopherin

Ran
GDP

RanGA P

cytoplasm

nucleus

nuclear
export
complex

Ran
GTP

Ran
GTP

cargo

cargo

Fig. 6.1 Overview of karyopherin-mediated nuclear import and export cycles. (a) In nuclear
import cycles, a karyopherin such as importin- β binds its cargo in the cytoplasm, often using

importin- as an adapter. The cargo:carrier complex then equilibrates between the cytoplasm and

the nucleus by diffusing through nuclear NPCs via weak interactions with nucleoporins that
contain a large number of repeating FG sequence motifs. When the karyopherin:cargo complex
reaches the nucleus it is dissociated by RanGTP binding to the karyopherin. The karyopherin:
RanGTP complex then diffuses through nuclear pores back to the cytoplasm where RanGAP
hydrolyzes the GTP leading to the dissociation of RanGDP and freeing the karyopherin to
participate in a further import cycle. (b) An analogous cycle is employed to export macromole-
cules such as proteins, t-RNA and pre-microRNAs from the nucleus. Here the cargo, RanGTP, and
karyopherin interact to for a ternary complex that diffuses through NPCs to the cytoplasm, where

α