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Published October 16, 2006
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Taking a Toll on neurons
B
stimulates TLR8. The treatment impeded the growth of neurites,
the branches that sprout from developing neurons, and
spurred some of the cells to kill themselves. An antibody that
latches onto TLR8 prevented both effects.
TLR8 usually raises the alarm by activating the signaling
pathway headed by NF-κB. But Ma et al. showed that NF-κB
remained off in neurons, indicating that the receptor acts in
these cells through an unidentified pathway. The researchers
speculate that TLR8 might serve as a danger detector
in neurons. If it senses infection or tissue
damage, it may deter neurons
from entering the trouble spot
by pruning their neurites or
triggering their suicide.
Toll-like receptor 8
(green) restrains cortical
neurons in the mouse embryo.
E n d o s o m e s b r i n g u p t h e re a r
ike jilted lovers, migrating cells need to let
go before they can move on. Slithering cells
get help from endosomes, via a receptor that
spurs tails to detach from the surface, as Sturge et al.
show on page 337.
Before it travels, a cell
breaks down the focal adhesions that link it to a
substrate or the adherens
junctions that bind it to
other cells. Activation of
Rho kinase (ROCK) aids
the process by enabling the
cell to disengage its rear end,
but what controls ROCK
isn’t certain. Sturge et al.
investigated the possible role
of endosomes, which get
involved in a multitude of
cell signaling events. They
find that an endosomelocalized receptor, called
Endo180, triggers migration
by breaking connections.
Internalized Endo180 is
Without Endo180 to release their tails, cells
known to set off migration.
elongate instead of migrating.
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JCB • VOLUME 175 • NUMBER 2 • 2006
The authors found that, when cancer cells were
depleted of Endo180, their front ends advanced, but
their tails remained anchored, and they stretched like
pieces of taffy. The loss of two other endosome
receptors, however, did not interfere with crawling.
Endo180 also disrupted adherens junctions.
Cranking up production of the protein cut the amount
of E-cadherin at these contact points, destabilizing
the connections between cells.
To determine whether Endo180 works by activating ROCK, the researchers measured phosphorylation
of myosin light chain-2, which retracts the cell’s tail.
ROCK adds phosphate groups to the myosin, but the
degree of phosphorylation plunged in the Endo180depleted cells. Just how the receptor activates ROCK
has not been worked out.
Endo180 cycles between endosomes and the cell
surface, and the study’s findings suggest that it is
the internal version that frees the tail. Endosomes
sporting Endo180 accumulate in the rear of cells.
And cells expressing a version of Endo180 that
remains at the plasma membrane failed to detach.
Extracellular collagen, Endo180’s favorite ligand,
was not necessary for deadhesion, but it is possible
that collagen produced within motile cells might
promote or limit its signaling capacity.
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attling pathogens and shaping neuronal growth seem
to have as much in common as accounting and skydiving. But both tasks involve one of the Toll-like proteins,
as Ma et al. report on page 209. The study is the first to discover
a function for a member of the Toll-like family within neurons.
Toll-like receptors (TLRs) enable mammalian immune cells
to identify interlopers. TLR8, for instance, recognizes RNA on
the loose, a sign of viral infection or cell destruction. The
Drosophila equivalents of the proteins, the Toll receptors, also
supervise synapse formation and axon growth, researchers
have discovered. Although previous studies had revealed that
mammalian neurons manufacture TLRs, no one had shown that
the molecules performed a job in these cells.
Ma et al. found that brain levels of TLR8 shot up in the early
mouse embryo and fell after birth, suggesting that the molecule
participates in nervous system development. To clarify its role, the
researchers dosed embryonic brain cells with a compound that
Published October 16, 2006
Text by Mitch Leslie
[email protected]
M e m b ra n e b a c k t ra c k i n g
he inner membrane of a chloroplast bristles with enzymes and other
proteins that are synthesized in the cytoplasm, but how they get into
position is uncertain. On page 249, Li and Schnell report that at least
some proteins pass through the inner membrane and reenter it from the back
side, rather than stopping on the way through.
Chloroplasts are swaddled by inner and outer membranes and contain a
third membrane system, the thylakoid, where photosynthesis occurs. Most
of the proteins in these membranes are made in the cytoplasm. Proteins can
slip directly into the outer membrane. But the journey to the inner membrane
is more complicated because proteins must traverse the outer membrane and
avoid piercing the thylakoid layer.
Li and Schnell followed the path of atTic40, which is part of an inner
membrane protein complex that helps usher others through the barrier. They
found that chloroplasts import an elongated version of atTic40 that accumulates
fully inside the chloroplast before moving back into the inner membrane.
The scientists also demonstrated that atTic40 can integrate into isolated
inner membranes, indicating that import of the proteins and their insertion into
the inner membrane are independent. Chloroplasts have thus evolved a sorting
system that can distinguish inner membrane and thylakoid proteins.
T
Gaps in the body wall (arrows) form in an embryo
lacking MyoD-producing epiblast cells.
Getting the embryo
into shape
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ome stem cells in the embryo have the
same effect as a personal trainer, show
Gerhart et al. on page 283. Although
they are candidates for forming muscle cells
themselves, they instead coax others to build
the muscle. Muscle-promoting cells might thus
emerge earlier in development than many
researchers thought.
When a chick embryo is only a twolayered disk, the upper layer called the epiblast
already houses a few cells that have turned on
the gene for MyoD, one of the supervisors for
muscle development. But the cells also manufacture another muscle stimulator, known as
Noggin. In the culture dish, these cells prod
unprogrammed cells to form muscle.
To investigate the cells’ function in bulking
up the embryo, Gerhart et al. tracked them
with antibodies. Most of the MyoD producers
ended up in the somites that give rise to muscle
throughout the body. The researchers then
destroyed the MyoD cells in the epiblast and
followed the developmental consequences. The
loss reduced the amount of skeletal muscle,
weakening the trunk muscles so much that organs bulged through the body wall.
Implanting beads saturated with Noggin
into the embryos corrected most defects. Noggin’s restorative ability indicates that the MyoDcarrying cells exert their impact mainly by spurring other cells to form muscle. The researchers
plan to determine whether these influential muscle progenitors have other functions during embryonic development.
M e l a n i n’s b a c k u p s
ports teams and melanin-making cells follow the same strategy: they
have substitutes in case a regular can’t perform. The cells rely on
redundant proteins to deliver enzymes for pigment production, as
Wasmeier et al. report on page 271. The results might clarify researchers’
understanding of an enigmatic class of cell organelles that participate in
everything from immunity to blood clotting.
The melanosomes that manufacture melanin are lysosome-related
organelles (LROs), which store and synthesize molecules in many cell
types. In platelets, for example, LROs house coagulation factors.
Researchers are still working out the details of LRO formation. One
mystery is how melanosomes stock up on
the enzymes tyrosinase and tyrosinaserelated protein-1 (Tyrp1), which are
essential for making melanin. Wasmeier et
al. investigated one protein that might have
a role in the process, Rab38.
Mice with a faulty version of Rab38 are
less dark than usual, but they are not albinos,
suggesting that another protein picks up the
pigmentation slack. The team identified the
backup as Rab38’s relative, Rab32. Cells
lacking both proteins are pale, and their
melanosomes show scant tyrosinase and Tyrp1.
The researchers tracked Rab38 and Rab32
to vesicles that often harbored tyrosinase or
Tyrp1. Wasmeier et al. conclude that the two
proteins somehow help pick up freshly minted
enzymes from the Golgi apparatus and bundle them into endosomes for
shipment to the melanosomes. How Rab38 and Rab32 work together and
Tyrosinase dispersal (top)
whether they help fashion other LROs remain open questions.
requires Rab32 (bottom).
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