Genetic and biochemical methods for identifying protein interaction motifs that confer nuclear localization

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Many proteins are precisely targeted to particular sub-cellular compartments by specific localization signals. Nuclear import of proteins is typically mediated by interaction with soluble cytosolic receptor proteins via nuclear localization signals (NLSs). Canonical NLSs contain either a short stretch of basic amino acids (monopartite) or two closely spaced short stretches of basic amino acids (bipartite). Despite the short length of canonical NLSs, which are as little as 4 or 5 amino acids in length, they make high affinity interactions in the cytosol with members of the importin family of NLS receptors (also known as karyopherins). Importins function as carriers to direct localization of the interacting cargo to the nucleus. The interaction of cargo/carrier complexes with components of the nuclear pore complex leads to nuclear import.