Intracellular Protein Traffic 
and Nuclear Organelles 
Gunter Blobel, M.D., Ph.D. — Investigator 
Dr. Blobel is also Professor of Cell Biology at the Rockefeller University. He received bis M.D. degree from 
the University of Tiibingen and his Ph.D. degree with Van Potter in oncology from the McArdle Laboratory 
at the University of Wisconsin-Madison. Thereafter, he did postdoctoral work with George Palade at 
Rockefeller. Dr. Blobel is a member of the National Academy of Sciences and of several other distinguished 
societies. He has received many honors, including the Gairdner Foundation Award. 
NUMEROUS structurally and functionally di- 
verse proteins can be translocated across a 
few distinct cellular membranes. It is now estab- 
lished that targeting to these membranes and 
translocation across them is specified by a mem- 
brane-specific "signal" sequence that is a tran- 
sient (or permanent) part of the protein to be 
translocated. The primary structure of numerous 
representatives for such a sequence has been es- 
tablished in our laboratory and by others. Present 
work focuses on the identification and character- 
ization of machinery involved in the recognition 
of a signal sequence, in its targeting to the proper 
membrane, and in protein translocation. Collec- 
tively, these components comprise what has been 
termed a protein translocon. 
Our laboratory is working on translocons for 
four distinct cellular entities: 1 ) the endoplasmic 
reticulum (ER) of animal (and yeast) cells, 
which is able to translocate proteins from the cy- 
tosol to the ER lumen; 2) bacterial plasma mem- 
branes (gram-negative bacteria), able to translo- 
cate proteins from the cytoplasm to the 
periplasmic space; 3) yeast mitochondria, able to 
translocate protein from the cytoplasm to the mi- 
tochondrial interior ("matrix") across outer and 
inner mitochondrial membranes; and 4) plant 
cell (pea and spinach) chloroplasts, able to trans- 
locate proteins from the cytoplasm to the chloro- 
plast interior ("stroma") across outer and inner 
chloroplast membranes. 
From studies on these four translocons so far, 
but especially from studies on the ER translocon, 
it is likely that a translocon is composed of at least 
four entities: 1) a soluble signal-recognition 
factor (SRF), 2) a homing receptor, 3) a signal 
sequence-gated protein-conducting channel, 
and 4) a signal-removing peptidase. The SRF has 
two functions: recognition of the signal sequence 
and targeting to the homing receptor, which is 
restricted in' its localization to a translocon- 
specific membrane. Interaction of the signal se- 
quence-SRF complex with the homing receptor 
leads to dissociation of the signal sequence and 
its presentation to a signal sequence receptor, 
which might be a subunit of the protein- 
conducting channel. This channel would close 
immediately following completion of transloca- 
tion, only to open again after presentation of an- 
other signal sequence. The signal peptidase 
would, in most cases, remove the signal sequence 
either during or shortly after translocation. 
In the case of the ER, the SRF was isolated and 
shown to be a ribonucleoprotein particle. Re- 
ferred to as a signal-recognition particle (SRP), 
this consists of one 7S RNA molecule and six dif- 
ferent proteins. Likewise, a homing receptor (re- 
ferred to as the SRP receptor) and a signal -remov- 
ing peptidase, a complex of five proteins, were 
isolated. More recently we were able to demon- 
strate the existence of a protein-conducting 
channel, using electrophysiological methods. 
The protein constituents of this channel remain 
to be identified. We have been able to solubilize 
the ER membranes by detergent and to reconsti- 
tute translocation-competent vesicles. Using this 
method, it should be possible to identify the 
channel proteins. 
We recently identified components of other 
translocons. An SRF was isolated for signal se- 
quence targeted to the bacterial plasma mem- 
brane. Moreover, we identified signal sequence- 
binding subunits for the mitochondrial and 
chloroplast translocons. These integral mem- 
brane proteins are located in contact sites be- 
tween outer and inner organelle membranes and 
are candidates for subunits of a protein-conduct- 
ing channel in the outer organelle membrane 
linked to a protein-conducting channel in the in- 
ner membrane. 
Our other major research effort focuses on the 
organelles associated with the cell's nuclear en- 
velope membranes. These organelles are thought 
to organize the large amount of information in 
the linear structure of the DNA into numerous 
structurally and functionally distinct three- 
dimensional superstructures, allowing only a lim- 
ited amount of that information to be expressed. 
Characterization of these organelles should ad- 
vance understanding of such fundamental pro- 
cesses as differential gene expression, cell differ- 
entiation, and development. 
Our efforts focus on the structural and func- 
tional characterization of two morphologically 
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