Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

TRANSPORT FROM THE ER THROUGH THE GOLGI APPARATUS
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vesicular tubular cluster
microtubule
COPII coat
motor
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ER
cis Golgi
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vesicular
tubular
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COPI
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retrieval transport
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Figure 13–24 Vesicular tubular clusters. (A) An electron micrograph of vesicular tubular
clusters forming around an exit site. Many of the vesicle-like structures seen in the micrograph
are cross sections of tubules that extend above and below the plane of this thin section and are
interconnected. (B) Vesicular tubular clusters move along microtubules to carry proteins from the
ER to the Golgi apparatus. COPI-coated vesicles mediate the budding of vesicles that return to the
ER from these clusters (and from the Golgi apparatus). (A, courtesy of William Balch.)
the electron microscope (Figure 13–24A). These clusters constitute a compartment
that is separate from the ER and lacks many of the proteins that function
in the ER. They are generated continually and function as transport containers
that bring material from the ER to the Golgi apparatus. The clusters move quickly
along microtubules to the Golgi apparatus with which they fuse (Figure 13–24B
and Movie 13.2).
As soon as vesicular tubular clusters form, they begin to bud off transport vesicles
of their own. Unlike the COPII-coated vesicles that bud from the ER, these
vesicles are COPI-coated (see Figure 13–24A). COPI-coated vesicles are unique in
MBoC6 m13.23/13.23
that the components that make up the inner and outer coat layers are recruited as
a preassembled complex, called coatomer. They function as a retrieval pathway,
carrying back ER resident proteins that have escaped, as well as proteins such
as cargo receptors and SNAREs that participated in the ER budding and vesicle
fusion reactions. This retrieval process demonstrates the exquisite control mechanisms
that regulate coat assembly reactions. The COPI coat assembly begins only
seconds after the COPII coats have been shed, and remains a mystery how this
switch in coat assembly is controlled.
The retrieval (or retrograde) transport continues as the vesicular tubular clusters
move toward the Golgi apparatus. Thus, the clusters continuously mature,
gradually changing their composition as selected proteins are returned to the ER.
The retrieval continues from the Golgi apparatus, after the vesicular tubular clusters
have delivered their cargo.
The Retrieval Pathway to the ER Uses Sorting Signals
The retrieval pathway for returning escaped proteins back to the ER depends on
ER retrieval signals. Resident ER membrane proteins, for example, contain signals
that bind directly to COPI coats and are thus packaged into COPI-coated transport
vesicles for retrograde delivery to the ER. The best-characterized retrieval signal
of this type consists of two lysines, followed by any two other amino acids, at the
extreme C-terminal end of the ER membrane protein. It is called a KKXX sequence,
based on the single-letter amino acid code.
Soluble ER resident proteins, such as BiP, also contain a short ER retrieval signal
at their C-terminal end, but it is different: it consists of a Lys-Asp-Glu-Leu or
a similar sequence. If this signal (called the KDEL sequence) is removed from BiP
by genetic engineering, the protein is slowly secreted from the cell. If the signal
is transferred to a protein that is normally secreted, the protein is now efficiently
returned to the ER, where it accumulates.