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Published October 16, 2006 In This Issue 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. L 194 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. Downloaded from on June 18, 2017 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 S Downloaded from on June 18, 2017 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). S IN THIS ISSUE • THE JOURNAL OF CELL BIOLOGY 195