SCIENTISTS DRAW THE MOST PRECISE MAP YET OF HUMAN DIASPORA
(Through studying DNA samples from a quarter of a million volunteers in different continents)HUMAN GEOGRAPHY IS MAPPED IN THE GENES
The genes of a European person can be enough to pinpoint their ancestry down to their home country, claim two new studies. By reading single-letter DNA differences in the genomes of thousands of Europeans, researchers can tell a Finn from a Dane and a German from a Brit. In fact a visual genetic map mirrors the geopolitical map of the continent...SPATIAL CONTROL OF BRANCHING WITHIN DENDRITIC ARBORS BY DYNEIN-DEPENDENT TRANSPORT OF RAB5-ENDOSOMES
Spatial control of branching within dendritic arbors by dynein-dependent transport of Rab5-endosomes
Nature Cell Biology 10, 1164 (2008). doi:10.1038/ncb1776
Authors: Daisuke Satoh, Daichi Sato, Taiichi Tsuyama, Motoki Saito, Hiroyuki Ohkura, Melissa M. Rolls, Fuyuki Ishikawa & Tadashi Uemura
Dendrites allow neurons to integrate sensory or synaptic inputs, and the spatial disposition and local density of branches within the dendritic arbor limit the number and type of inputs. Drosophila melanogaster dendritic arborization (da) neurons provide a model system to study the genetic programs underlying such geometry in vivo. Here we report that mutations of motor-protein genes, including a dynein subunit gene (dlic) and kinesin heavy chain (khc), caused not only downsizing of the overall arbor, but also a marked shift of branching activity to the proximal area within the arbor. This phenotype was suppressed when dominant-negative Rab5 was expressed in the mutant neurons, which deposited early endosomes in the cell body. We also showed that 1) in dendritic branches of the wild-type neurons, Rab5-containing early endosomes were dynamically transported and 2) when Rab5 function alone was abrogated, terminal branches were almost totally deleted. These results reveal an important link between microtubule motors and endosomes in dendrite morphogenesis.
THE TYPE I TGF-? RECEPTOR ENGAGES TRAF6 TO ACTIVATE TAK1 IN A RECEPTOR KINASE-INDEPENDENT MANNER
The type I TGF-β receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner
Nature Cell Biology 10, 1199 (2008). doi:10.1038/ncb1780
Authors: Alessandro Sorrentino, Noopur Thakur, Susanne Grimsby, Anders Marcusson, Verena von Bulow, Norbert Schuster, Shouting Zhang, Carl-Henrik Heldin & Maréne Landström
Transforming growth factor-β (TGF-β) is a multifunctional cytokine that regulates embryonic development and tissue homeostasis; however, aberrations of its activity occur in cancer. TGF-β signals through its Type II and Type I receptors (TβRII and TβRI) causing phosphorylation of Smad proteins. TGF-β-associated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family, was originally identified as an effector of TGF-β-induced p38 activation. However, the molecular mechanisms for its activation are unknown. Here we report that the ubiquitin ligase (E3) TRAF6 interacts with a consensus motif present in TβRI. The TβRI–TRAF6 interaction is required for TGF-β-induced autoubiquitylation of TRAF6 and subsequent activation of the TAK1–p38/JNK pathway, which leads to apoptosis. TβRI kinase activity is required for activation of the canonical Smad pathway, whereas E3 activity of TRAF6 regulates the activation of TAK1 in a receptor kinase-independent manner. Intriguingly, TGF-β-induced TRAF6-mediated Lys 63-linked polyubiquitylation of TAK1 Lys 34 correlates with TAK1 activation. Our data show that TGF-β specifically activates TAK1 through interaction of TβRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6.
DYNEIN IS REQUIRED FOR POLARIZED DENDRITIC TRANSPORT AND UNIFORM MICROTUBULE ORIENTATION IN AXONS
Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons
Nature Cell Biology 10, 1172 (2008). doi:10.1038/ncb1777
Authors: Yi Zheng, Jill Wildonger, Bing Ye, Ye Zhang, Angela Kita, Susan H. Younger, Sabina Zimmerman, Lily Yeh Jan & Yuh Nung Jan
Axons and dendrites differ in both microtubule organization and in the organelles and proteins they contain. Here we show that the microtubule motor dynein has a crucial role in polarized transport and in controlling the orientation of axonal microtubules in Drosophila melanogaster dendritic arborization (da) neurons. Changes in organelle distribution within the dendritic arbors of dynein mutant neurons correlate with a proximal shift in dendritic branch position. Dynein is also necessary for the dendrite-specific localization of Golgi outposts and the ion channel Pickpocket. Axonal microtubules are normally oriented uniformly plus-end-distal; however, without dynein, axons contain both plus- and minus-end distal microtubules. These data suggest that dynein is required for the distinguishing properties of the axon and dendrites: without dynein, dendritic organelles and proteins enter the axon and the axonal microtubules are no longer uniform in polarity.
NASA ‘REVIEWS SHUTTLE SHELF-LIFE’
Nasa is to see if the space shuttle can fly beyond its 2010 planned retirement, reports say, despite safety fears.‘BIG DRY’ TURNS FARMS INTO DESERTS
Australian farmers are watching helplessly as the 'Big Dry' turns once lush grazing land into an arid desert, the BBC's Nick Bryant reports.A FEATURE-BASED APPROACH TO MODELING PROTEIN–DNA INTERACTIONS
PLoS Comput Biol, Vol. 4, No. 8. (2008), e1000154.Transcription factor (TF) binding to its DNA target site is a fundamental regulatory interaction. The most common model used to represent TF binding specificities is a position specific scoring matrix (PSSM), which assumes independence between binding positions. However, in many cases, this simplifying assumption does not hold. Here, we present feature motif models (FMMs), a novel probabilistic method for modeling TF–DNA interactions, based on log-linear models. Our approach uses sequence features to represent TF binding specificities, where each feature may span multiple positions. We develop the mathematical formulation of our model and devise an algorithm for learning its structural features from binding site data. We also developed a discriminative motif finder, which discovers de novo FMMs that are enriched in target sets of sequences compared to background sets. We evaluate our approach on synthetic data and on the widely used TF chromatin immunoprecipitation (ChIP) dataset of Harbison et al. We then apply our algorithm to high-throughput TF ChIP data from mouse and human, reveal sequence features that are present in the binding specificities of mouse and human TFs, and show that FMMs explain TF binding significantly better than PSSMs. Our FMM learning and motif finder software are available at http://genie.weizmann.ac.il/.
Eilon Sharon, Shai Lubliner, Eran Segal
