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On page 77, Farina et al. get a handle on RNA localization machinery by proving that an RNA-binding protein is essential for both mRNA transport and cell motility.
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The cell motility connection comes about because localization of the ?-actin mRNA to the lamellae is required for cell polarity and motility in fibroblasts. The new results show that this localization depends on ZBP1, a protein associated with cytoplasmic granules that contain the actin mRNA. ZBP1 bound to the mRNA through two COOH-terminal KH domains that were required for granule formation and attachment to the actin cytoskeleton. NH2-terminal regions of ZBP1 were necessary for granule localization in the lamellae.6 z& x& n5 l# ~! P
" d9 M: U& z s" g" R/ _4 H7 pDominant–negative ZBP1 constructs that mislocalized actin RNA inhibited fibroblast motility. Since mRNAs for some actin-associated proteins, such as ARP3, also contain ZBP1-binding sequences, the authors believe that ZBP1 may link several messages involved in motility to a transport complex. But ZBP1 may be more than just a scaffold: a ZBP1 homologue has been linked to translational repression of the insulin-related growth factor. Perhaps ZBP1 also ensures that the actin mRNA is not translated until it reaches its ultimate destination.The group plans to purify ZBP1- associated proteins in the complex to identify the motor responsible for actin-based transport. ZBP1 is also known to be associated with microtubules in neurons, so it may connect to different motors depending on the cell type.(Lamella-localized ZBP1 (white) granules ) |
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发表于 2009-3-6 00:35
发表于 2015-6-13 21:21
