Question

compare and contrast protein import into the ER and into the nucleus. List at least two major differences in the mechanisms, and speculate why the ER mechanism might not work for nuclear import and vice versa.

Answer 1

• Protein import into the ER: ER, golgi complex, endosome, lysosome and plasma membrane are collectively referred as endomembranous system. Synthesis of all proteins of endomembranous system starts in cytoplasm and then completed on RER membrane. All proteins of endomembranous system contain a signal sequence, present at N terminal that appear in early steps of translation. As signal sequence emerge out of the ribosomes, signal recognition particle (SRP) binds to the ribosomes. GTP bound SRP catalyse translocation of whole complex (ribosome, mRNA and nascent polypeptide) to the RER membrane. On RER membrane ribosome interact with translocase and then SRP hydrolyse their GTP and dissociate. Now ribosome restarts translation and growing polypeptide enter in ER lumen. In lumen signal sequence is removed by signal peptidase enzyme and then expose another targetting signal.
• Protein import into the nucleus: Mediated by a specialized translocator called nuclear pore complex (NPC). NPC forms a selective gate by which selective molecules such as proteins, RNA and ribosomes can enter/exit thus NPC involves in bidirectional transportation. Every protein of nucleus has a signal sequence that guide their transportation called nuclear localization signal. Transportation is mediated by a cytosolic receptor protein called importin. Transportation direction and transportation rate of proteins is regulated by a monomeric G protein called Ran. Ran exist in two states: Ran-GDP form in cytoplasm and Ran-GTP form in nucleus. A gradient of Ran-GDP/GTP exist across the membrane and primarily maintain direction of nuclear transportation.

Two major differences in the mechanisms are:

1. ER transport is a type of membranous transportation whereas nuclear transport is a type of gated transportation.

2. All proteins of nucleus, mitochondria, chloroplast and mitochondria are synthesized in cytoplasm and then these organelles selectively import their proteins from cytoplasm whereas proteins of ER, golgi complex, lysosome, plasma membrane and all secretory proteins are synthesized on RER membrane.