MANY freshly made proteins are carried in tiny bags made from cell membrane
to the place in the cell where they are needed. This delivery system is critical
to the cell鈥檚 survival. But how do those packages find the right destination?
New findings suggest that they carry an address in the form of protruding
protein arms.
The fatty bags, called vesicles, shuttle proteins between the cell鈥檚 many
membrane-bound compartments. For example, many newly made proteins enter the
endoplasmic reticulum (ER). Vesicles that bud off the ER carry these proteins to
the Golgi apparatus, where they are modified. Others take proteins to vacuoles,
the cell鈥檚 trash cans, while yet others deliver proteins to the cell鈥檚 outer
membrane. When a vesicle reaches its destination, it fuses with the membrane and
disgorges its contents.
Driving this fusion are two proteins called v-SNARE and t-SNARE, which
protrude from the membranes of both the vesicle and target and lock arms in a
sort of secret handshake. James Rothman and his colleagues at the Memorial
Sloan-Kettering Cancer Center in New York and other researchers have reproduced
the fusion event in a test tube by putting v-SNARE on one artificial vesicle and
t-SNARE on another.
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Fusion is one thing, but how does a vesicle 鈥渒now鈥� it鈥檚 at the right target?
Is this also the work of the SNAREs? Rothman knew that each compartment marks
the vesicles it produces with a specific v-SNARE protein and that different
targets have different t-SNAREs. So using the test tube fusion system, he and
his team tested the ability of different SNARE pairs to drive fusion.
The SNAREs turned out to be remarkably choosy. As expected from their known
travel routes, vesicles with ER v-SNARE fused only with vesicles displaying the
Golgi t-SNARE. Other vesicles that fused carried SNAREs for vacuole-to-vacuole
and Golgi-to-outer-membrane transmission. But combinations for routes never seen
in the cell鈥攕uch as ER-to-ER鈥攄id not fuse.
鈥淭his is the apex of simplicity,鈥� says Rothman. 鈥淵ou can reduce specificity
of vesicle transport to protein-mediated fusion.鈥� Rothman says this doesn鈥檛 mean
other proteins don鈥檛 help guide the vesicles, but their role may be
redundant.
Only one combination of SNAREs that was not expected to work did cause
vesicles to fuse. This was the SNARE pair representing transport from vacuole to
cell membrane. Although no one has seen this route in yeast鈥攆rom which
Rothman took the proteins鈥攊t is well known in animal cells and slime
moulds.