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

706 Chapter 13: Intracellular Membrane Traffic
Table 13–1 Subcellular Locations of Some Rab Proteins
Protein
Rab1
Rab2
Rab3A
Rab4/Rab11
Rab5
Rab6
Rab7
Rab8
Rab9
Organelle
ER and Golgi complex
cis Golgi network
Synaptic vesicles, secretory vesicles
Recycling endosomes
Early endosomes, plasma membrane, clathrin-coated vesicles
Medial and trans Golgi
Late endosomes
Cilia
Late endosomes, trans Golgi
cytosol; in their GTP-bound state, they are active and tightly associated with the
membrane of an organelle or transport vesicle. Membrane-bound Rab-GEFs
activate Rab proteins on both transport vesicle and target membranes; for some
membrane fusion events, activated Rab molecules are required on both sides
of the reaction. Once in the GTP-bound state and membrane-bound through a
now-exposed lipid anchor, Rab proteins bind to other proteins, called Rab effectors,
which are the downstream mediators of vesicle transport, membrane tethering,
and membrane fusion (Figure 13–16). The rate of GTP hydrolysis sets the
concentration of active Rab and, consequently, the concentration of its effectors
on the membrane.
In contrast to the highly conserved structure of Rab proteins, the structures
and functions of Rab effectors vary greatly, and the same Rab proteins can often
bind to many different effectors. Some Rab effectors are motor proteins that propel
vesicles along actin filaments or microtubules to their target membrane. Others
are tethering proteins, some of which have long, threadlike domains that serve
as “fishing lines” that can extend to link two membranes more than 200 nm apart;
other tethering proteins are large protein complexes that link two membranes
that are closer together and interact with a wide variety of other proteins that facilitate
the membrane fusion step. The tethering complex that docks COPII-coated
cargo receptor
Rab-GTP
v-SNARE
TETHERING
Rab effector
(tethering protein)
t-SNARE
CYTOSOL
target membrane
cargo
DOCKING
trans-SNARE
complex
Rab-GDP
FUSION
GDI
Figure 13–16 Tethering of a transport
vesicle to a target membrane. Rab
effector proteins interact with active Rab
proteins (Rab-GTPs, yellow) located on
the target membrane, vesicle membrane,
or both, to establish the first connection
between the two membranes that are
going to fuse. In the example shown here,
the Rab effector is a filamentous tethering
protein (dark green). Next, SNARE proteins
on the two membranes (red and blue) pair,
docking the vesicle to the target membrane
and catalyzing the fusion of the two
apposed lipid bilayers. During docking and
fusion, a Rab-GAP (not shown) induces the
Rab protein to hydrolyze its bound GTP to
GDP, causing the Rab to dissociate from
the membrane and return to the cytosol
as Rab-GDP, where it is bound by a GDI
protein that keeps the Rab soluble and
inactive.