Resident integral proteins of the inner nuclear membrane (INM) are synthesized 
as membrane-integrated proteins on the peripheral endoplasmic reticulum (ER) and 
are transported to the INM throughout interphase using an unknown trafficking 
mechanism. To study this transport, we developed a live cell assay that measures 
the movement of transmembrane reporters from the ER to the INM by 
rapamycin-mediated trapping at the nuclear lamina. Reporter constructs with 
small (<30 kD) cytosolic and lumenal domains rapidly accumulated at the INM. 
However, increasing the size of either domain by 47 kD strongly inhibited 
movement. Reduced temperature and ATP depletion also inhibited movement, which 
is characteristic of membrane fusion mechanisms, but pharmacological inhibition 
of vesicular trafficking had no effect. Because reporter accumulation at the INM 
was inhibited by antibodies to the nuclear pore membrane protein gp210, our 
results support a model wherein transport of integral proteins to the INM 
involves lateral diffusion in the lipid bilayer around the nuclear pore 
membrane, coupled with active restructuring of the nuclear pore complex.