Compare and contrast protein import into the ER and into the nucleus. List at least two major differences in the mechanisms and speculate on why the nuclear mechanism might not work for ER import. Solution The Proteins are imported into the nucleus from the cytoplasm only after thay have been synthesized,folded and properly assembled into complexes. They carry a sequence of amino acids that acts as a tag called as Nuclear localization signals (NLS) ,bound by importins. In contrast, all the unfolded polypeptide chains will be imported or translocated into ER as they are been made by the ribosomes. Though ribosomes function in the cytosol they are assembled in the nucleus where as the enzyme complexes function in the nucleus and assembles in the cytosol. But, both these ribosomes and enzyme complexes are transported through a nuclear pore intact. These Nuclear pores are gates, always opened for small molecules; in contrast, translocation channels in the ER membrane will be normally closed and open only after the ribosome has attached to the membrane. The ER membrane remains impermeable to small molecules during the translocation process, as the ER is a major store for Ca2+ ions in the cell, and Ca2+ ions released into the cytosol must be tightly controlled. Nuclear localization signals (NLS) are not cleaved off after the protein is imported into the nucleus; in contrast, ER signal peptides are usually cleaved off. Nuclear localization signals (NLS) are needed inorder to reimport nuclear proteins repeatedly after they have been released into the cytosol i.e during mitosis, when the nuclear envelop breaks down..