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An efficient trucking system might involve a small number of
vesicles specialized to carry just FcRn, so Björkman expected to
see a few vesicles containing a lot of FcRn and antibody. Instead,
cells had a lot of vesicles holding only a little of the cargo.
Moreover, the vesicles weren't neat spheres. They were “looped and
bent, and twisted around each other. They almost tied
themselves in knots,” says Björkman. “It was a tangled mess I
wasn't expecting.” Previous results from two-dimensional
imaging had suggested a more orderly grouping of small vesicles,
where vesicles typically travel across cells on protein tracks.
But in Björkman's observations few vesicles were lined up with
these tracks. She suspects that once the longer tubes expunge
the smaller vesicles, those small vesicles move randomly through
the cell until they collide with the membrane.
The delivery step also bore a surprise. As expected, vesicles
arrived at the blood vessel side of the cell and fused with the
membrane to release their antibody load. But the vesicles also
carried the tell-tale hexagons and pentagons of clathrin, a molecule
that helps form vesicles by constructing a cage around them.
Conventional wisdom holds that vesicles have to shed this cage
before they deliver their cargo, so Björkman was surprised to see
clathrin there. The observation might reveal a new mechanism
for releasing cargo, says Björkman. For instance, vesicles might
shed only a small part of their clathrin coating to quickly jettison
antibodies and immediately return to pick up a new load.
Björkman is now after a more detailed view of antibody
transport, employing other methods to witness transport in
action. “In EM, everything is in a vacuum; nothing is alive,”
says Björkman. “But in fluorescent live imaging we can take 5
frames per second and watch vesicles move.” Gazing at the
mysteries those movies hold could provide action-packed
evidence for some of Björkman's speculations.