Characteristics of the Endoplasmic Reticulum
in “Professional Secretory Cells”
Proteins that are secreted outside the cell are synthesized in the endoplasmic reticulum （ Endoplasmic Reticulum ; ER）Once synthesis has started on the ER
membrane, the synthesized polypeptides are immediately transported into the ER, where it undergoes
various quality control processes such as folding into the native structure and glycosylation. In
other words, being transported to the ER is the first important step in the biosynthesis of
procollagen molecules. Fibroblasts that secrete a lot of procollagen molecules contain a large
amount of ER, and in particular, they have a well-developed rough ER*.
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Figure 1 shows an example of human fibroblasts observed by electron microscope. The rER
of human fibroblasts are associated with many ribosome particles (polyribosomes) that are associated
with mRNA to form beads on a thread-like structure (Figure 1a). When observed at a higher
magnification, it can be seen that each polyribosome contains more than 20 particulate structures
(Figure 1b). It has been found that these long polyribosomes associated with the mRNA on endoplasmic
reticulum membrane play a major role in the highly efficient secretion of procollagen by human
fibroblasts [1, 3].
Figure 1: Electron microscopic images of human fibroblasts, modified from [3]
When the surface of the endoplasmic reticulum membrane of human fibroblasts cultured under
conditions that promote large-scale secretion of procollagen is observed using an electron
microscope, many long-chain polyribosomes consisting of linked ribosome particles are
observed.
p180/RRBP-1 protein, which is important for the formation
of long polyribosomes in the endoplasmic reticulum
The formation of long polyribosomes, as shown in Figure 1, is inhibited when the culture conditions
are changed to suppress procollagen secretion. We have focused on the p180 protein (Ribosome-binding
protein 1, encoded by the RRBP1 gene in human), hereafter, p180, of the ER membrane as a protein
that plays a quite important role in activating procollagen secretion, and have been analyzing its
molecular mechanism in detail [2-5].
We found that p180 is essential for the formation of long-chain polyribosomes in the ER membrane
during collagen secretion activation, and p180 exerts a selective effect. For example, when the p180
expression level is lowered, the amount of collagen and fibronectin secreted decreases, but the
amount of other secreted proteins (such as tissue inhibitor of metalloproteinase-1, TIMP-1 and
Matrix metalloproteinase-2, MMP-2) are not decreased [2]. When we analyzed the mechanism underlying
this selective effect of p180/RRBP1, we identified a novel factor, the splicing factor, SF3b4, that
works in cooperation with p180 works in collaboration with a novel factor, SF3b4 [1]. SF3b4 is
normally found in the nucleus, but in fibroblasts that actively secrete collagen, it is also found
in the ER, and when the SF3b4 content decreases, collagen secretion also decreases. Various analyses
have shown that SF3b4, in cooperation with p180, is an essential factor in processes such as the
formation of long polyribosomes, including procollagen mRNA, and the transfer of mRNA to the ER [1].
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