Functional association of Sun1 with nuclear pore complexes

Sun1 and 2 are A-type lamin-binding proteins that, in association with nesprins, form a link between the inner nuclear membranes (INMs) and outer nuclear membranes of mammalian nuclear envelopes. Both immunofluorescence and immunoelectron microscopy reveal that Sunl but not Sun2 is intimately associated with nuclear pore complexes (NPCs). Topological analyses indicate that Sunl is a type II integral protein of the INM. Localization of Sun 1 to the INM is defined by at least two discrete regions within its nucleoplasmic domain. However, association with NPCs is dependent on the synergy of both nucleoplasmic and lumenal domains. Cells that are either depleted of Sun1 by RNA interference or that overexpress dominant-negative Sunl fragments exhibit clustering of NPCs. The implication is that Sun 1 represents an important determinant of NPC distribution across the nuclear surface.