Rough ER

▲ FIGURE 17-16 Role of the KDEL receptor in retrieval of ER-resident luminal proteins from the Golgi.

ER luminal proteins, especially those present at high levels, can be passively incorporated into COPII vesicles and transported to the Golgi (steps 1 and 2|). Many such proteins bear a C-terminal KDEL (Lys-Asp-Glu-Leu) sequence (red) that allows them to be retrieved. The KDEL receptor, located mainly in the c/s-Golgi network and in both COPII and COPI vesicles, binds proteins bearing the KDEL sorting signal and returns them to the ER (steps 3 and 4|). This retrieval system prevents depletion of ER luminal proteins such as those needed for proper folding of newly made secretory proteins. The binding affinity of the KDEL receptor is very sensitive to pH. The small difference in the pH of the ER and Golgi favors binding of KDEL-bearing proteins to the receptor in Golgi-derived vesicles and their release in the ER. [Adapted from J. Semenza et al., 1990, Cell 61:1349.]

Anterograde Transport Through the Golgi Occurs by Cisternal Progression

At one time it was thought that small transport vesicles carry secretory proteins from the cis- to the medial-Golgi and from the medial- to the trans-Golgi. Indeed, electron microscopy reveals many small vesicles associated with the Golgi complex that move proteins from one Golgi compartment to another (Figure 17-17). However, these vesicles most likely mediate retrograde transport, retrieving ER or Golgi enzymes from a later compartment and transporting them to an earlier compartment in the secretory pathway. In this way enzymes that modify secretory proteins come to be localized in the correct compartment.

The first evidence that the forward transport of cargo proteins from the cis- to the trans-Golgi occurs by a non-vesicular mechanism, called cisternal progression, came from careful microscopic analysis of the synthesis of algal scales. These cell-wall glycoproteins are assembled in the cis-Golgi into large complexes visible in the electron microscope. Like other secretory proteins, newly made scales move from the cis- to the trans-Golgi, but they can be 20 times larger than the usual transport vesicles that bud from Golgi cisternae. Similarly, in the synthesis of collagen by fibroblasts, large aggregates of the procollagen precursor often form in the

▲ EXPERIMENTAL FIGURE 17-17 Electron micrograph of the Golgi complex in an exocrine pancreatic cell reveals both anterograde and retrograde transport vesicles. A large secretory vesicle can be seen forming from the trans-Golgi network. Elements of the rough ER are on the left in this micrograph. Adjacent to the rough ER are transitional elements lumen of the cis-Golgi (see Figure 6-20). The procollagen aggregates are too large to be incorporated into small transport vesicles, and investigators could never find such aggregates in transport vesicles. These observations suggested that the forward movement of these and perhaps all secretory proteins from one Golgi compartment to another does not occur via small vesicles.

In one test of the cisternal progression model, collagen folding was blocked by an inhibitor of proline hydroxy-lation, and soon all pre-made, folded procollagen aggregates were secreted from the cell. When the inhibitor was removed, newly made procollagen peptides folded and then formed aggregates in the cis-Golgi that subsequently could be seen to move as a "wave" from the cis- through the medial-Golgi cisternae to the trans-Golgi, followed by secretion and incorporation into the extracellular matrix. In these experiments procollagen aggregates were never visible in small transport vesicles. Numerous controversial questions concerning membrane flow within the Golgi stack remain unresolved. Nonetheless, the observed movement of very large macromolecular assemblies through the Golgi stack and the evidence described previously that COPI vesicles mediate retrograde transport have led most researchers in the field to favor the cisternal progression model.

from which smooth protrusions appear to be budding. These buds form the small vesicles that transport secretory proteins from the rough ER to the Golgi complex. Interspersed among the Golgi cisternae are other small vesicles now known to function in retrograde, not anterograde, transport. [Courtesy G. Palade.]

Was this article helpful?

0 0
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment