FIG. 8.

The mechanism underlying nucleolar localization may include a nucleolus-targeting B domain, a retention signal, and an NpLS coupled with a regulatory module. In addition to the commonly identified, positively charged (+) B domain, the static and dynamic distribution of nucleolar proteins between the nucleolus (rounded rectangles) and the nucleoplasm can be further modified by a retention signal, an NpLS, or a combination of both. By itself, the B domain can accumulate in the nucleolus with a short nucleolar retention time, represented by thick arrows (A). The addition of a retention signal (RS) can slow down the protein exchange rate, indicated by thin arrows, of both nucleolar (B) and nucleoplasmic proteins (C). The ability of the NpLS to detain proteins with nucleolar localization capability in the nucleoplasm can be constitutively active (D) or regulated by a regulatory module (E). For NS and Ngp1, the G domain functions as both the retention signal and the regulatory module for the NpLS.