Intracellular Protein Traffic and Nuclear Organelles 
Our efforts focus on the structural and func- 
tional characterization of two morphologically 
distinct structures. One, the nuclear pore com- 
plex, is located in the nuclear envelope. We spec- 
ulate that this organelle is involved in "gene gat- 
ing" — i.e., each pore complex is attached to a set 
of actively transcribed genes. We have identified 
and isolated several proteins of the pore complex 
and have recently established the primary struc- 
ture of a large membrane protein that is specifi- 
cally located in the pore membrane domain of 
the nuclear envelope membrane. We are also us- 
ing cell-free systems for protein uptake into the 
nucleus to isolate the hypothetical SRF, the hom- 
ing receptor, and the so-called transporter of the 
pore complex. 
The other morphologically distinct structure 
associated with the nuclear envelope that we are 
studying is the nuclear lamina, a fibrous mesh- 
work associated with the nuclear side of the inner 
nuclear envelope membrane. The lamina consists 
of three proteins, which we have termed lamins 
A, B, and C. We have speculated that the nuclear 
lamina is involved in the three-dimensional orga- 
nization of nontranscribed chromatin. 
By molecular cloning and cDNA sequencing of 
the three lamins, we and others showed recently 
that these proteins are members of the interme- 
diate filament protein family. We demonstrated 
that lamin B binds to the carboxyl-terminal por- 
tion of cytoplasmic intermediate filament pro- 
teins and that ankyrin, a protein associated with 
the plasma membrane, binds to the amino-termi- 
nal portion of cytoplasmic intermediate filament 
proteins. Recently, we have investigated the in- 
teraction of such a protein with nuclear lamin B 
in more detail and have localized the interacting 
region to the near carboxyl-terminal segment of 
these proteins. Interestingly, a synthetic peptide, 
representing this lamin B-binding site of the cy- 
toplasmic intermediate filament protein, when 
microinjected into cells, led to the detachment of 
intermediate filaments from the nucleus. 
These data indicate a direct connection be- 
tween the plasma membrane skeleton (ankyrin) , 
the cytoskeleton (intermediate filaments), and 
the peripheral nucleoskeleton (lamina) through 
the nuclear pore. Moreover, we have recently 
identified a lamin B receptor in the inner nuclear 
membrane. Its primary structure has been deter- 
mined by molecular cloning and cDNA sequenc- 
ing. It has a number of interesting sites, suggest- 
ing that it may not only interact with lamin B but 
also with DNA. 
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