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Ciliary dysfunction impairs beta-cell insulin secretion and promotes development of type 2 diabetes in rodents
Cilia are hair-like protuberances on the cellular surface that have been implicated in sensing and signal transduction. Here Gerdes et al. show cilia are involved in insulin signalling and secretion in pancreatic β-cells of rodents, and suggest that ciliary dysfunction could contribute to type 2 diabetes.
- Jantje M. Gerdes
- , Sonia Christou-Savina
- & Per-Olof Berggren
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MTCL1 crosslinks and stabilizes non-centrosomal microtubules on the Golgi membrane
Microtubules that nucleate from the surface of the Golgi network are important for polarized trafficking and cell migration. Sato et al.find that these microtubules are crosslinked and stabilized by the microtubule-binding protein MTCL1, and show that this activity is required for Golgi structure and function.
- Yoshinori Sato
- , Kenji Hayashi
- & Atsushi Suzuki
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| Open AccessKinesin-14 and kinesin-5 antagonistically regulate microtubule nucleation by γ-TuRC in yeast and human cells
Mitotic spindle assembly requires strict control of microtubule nucleation by γ-tubulin ring complexes. Olmsted et al. report that the kinesin-like proteins Pkl1 and Cut7 antagonistically regulate nucleation in fission yeast, and show that a Pkl1 peptide blocks spindle assembly in human cancer cells.
- Zachary T. Olmsted
- , Andrew G. Colliver
- & Janet L. Paluh
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Arl3 and LC8 regulate dissociation of dynactin from dynein
Cargo is transported through the cell on microtubules, but the regulatory mechanism controlling release of dynactin-bound cargo from dynein is not known. Here, Jin et al.uncover roles for ADP-ribosylation factor-like 3 (Arl3) and dynein light chain LC8 in unloading cargo from microtubules.
- Mingyue Jin
- , Masami Yamada
- & Shinji Hirotsune
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| Open AccessXTACC3–XMAP215 association reveals an asymmetric interaction promoting microtubule elongation
chTOG, a microtubule polymerase, interacts with TACC3 during mitosis to regulate spindle formation. By studying their Xenopus homologues, Mortuza et al. discover that one TACC3 recruits two chTOG molecules to the spindle, increasing its local concentration and promoting microtubule elongation.
- Gulnahar B. Mortuza
- , Tommaso Cavazza
- & Guillermo Montoya
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Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation
The oligomeric Dam1 complex mediates microtubule attachment to kinetochores during mitosis; however, the significance of its oligomeric structure remains unclear. Umbreit et al. show that Dam1 oligomerization is required for microtubules to form attachments that are robust against tension.
- Neil T. Umbreit
- , Matthew P. Miller
- & Trisha N. Davis
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Basal foot MTOC organizes pillar MTs required for coordination of beating cilia
Coordinated beating of motile cilia is important to clear mucus from the airway. Here, Clare et al. show that galectin-3 at the base of motile cilia in the trachea is important for connecting cortical microtubules to the basal body, and subsequent organization and coordination of beating cilia.
- Daniel K. Clare
- , Jérémy Magescas
- & Delphine Delacour
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| Open AccessAn assay to image neuronal microtubule dynamics in mice
Microtubule dynamics in neurons play critical roles in physiology, injury and disease. Here the authors develop a transgenic mouse line expressing a fluorescently tagged version of the microtubule binding protein EB3, and using a range of imaging techniques, study microtubule dynamics under normal and injury conditions in living mice.
- Tatjana Kleele
- , Petar Marinković
- & Thomas Misgeld
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The subcortical maternal complex controls symmetric division of mouse zygotes by regulating F-actin dynamics
The mammalian subcortical maternal complex is composed of maternally expressed proteins and required for mouse early embryonic cell division. Here the authors show that the complex functions to control spindle positioning through regulation of the actin cytoskeleton.
- Xing-Jiang Yu
- , Zhaohong Yi
- & Lei Li
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Mechanistic insight into GPCR-mediated activation of the microtubule-associated RhoA exchange factor GEF-H1
The RhoGEF GEF-H1 is normally sequestered on microtubules via binding dynein light-chain Tctex-1, and is activated by microtubule depolymerization. Here, Meiri et al. describe a new model of GEF-H1 activation by GPCRs, whereby both the Gα and Gβγ subunits bind to GEF-H1 and Tctex-1, respectively, to displace GEF-H1 from intact microtubules.
- David Meiri
- , Christopher B. Marshall
- & Robert Rottapel
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Dynactin functions as both a dynamic tether and brake during dynein-driven motility
It remains unclear how the dynactin complex activates cytoplasmic dynein motor proteins. Ayloo et al.use single molecule imaging to observe dynein–dynactin behaviour on microtubules, and show that dynactin recruits dynein to microtubules and acts as a brake to slow the motor.
- Swathi Ayloo
- , Jacob E. Lazarus
- & Erika L. F. Holzbaur
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| Open AccessActin–microtubule coordination at growing microtubule ends
The structural cross-talk between components of the eukaryotic cytoskeleton remains poorly understood. Here the authors engineer an actin-binding microtubule tip-tracking protein that guides microtubule growth along actin bundles, and allows microtubule growing ends to pull and bundle actin filaments.
- Magdalena Preciado López
- , Florian Huber
- & Marileen Dogterom
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The deubiquitinating enzyme CYLD controls apical docking of basal bodies in ciliated epithelial cells
Mutations in the deubiquitinase gene CYLD are associated with cylindromatosis, a disease characterized by the development of skin appendage tumours. Eguether et al.discover that CYLD localizes to centrosomes and is required for basal body migration and docking, providing insight into its tumour suppressor activity.
- Thibaut Eguether
- , Maria A. Ermolaeva
- & Anne-Marie Tassin
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Documentation and localization of force-mediated filamin A domain perturbations in moving cells
Biosensors designed to respond to mechanical force in cells have provided insights into the force landscape within a cell. Here, Nakamura et al. design a FRET probe in the actin crosslinking protein filamin A and show that it unfolds under force only in newly protruding regions of the cell.
- Fumihiko Nakamura
- , Mia Song
- & Thomas P. Stossel
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Tension on the linker gates the ATP-dependent release of dynein from microtubules
Unlike most processive motor proteins, the stepping motion of cytoplasmic dynein’s two linked motor domains is not precisely coordinated. Cleary et al.show that the ATPase activity of just one head is required for processive movement, and that tension on the linker gates the release of the motor from microtubules.
- Frank B. Cleary
- , Mark A. Dewitt
- & Ahmet Yildiz
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The condensin component NCAPG2 regulates microtubule–kinetochore attachment through recruitment of Polo-like kinase 1 to kinetochores
Polo-like kinase 1 (PLK1) regulates the spindle assembly checkpoint and is recruited to prometaphase kinetochores. Kim et al.show that the condensin subunit NCAPG2 is required for stable interaction of PLK1 with kinetochores and for proper chromosome segregation.
- Jae Hyeong Kim
- , Jaegal Shim
- & Kyung-Tae Kim
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MCIDAS mutations result in a mucociliary clearance disorder with reduced generation of multiple motile cilia
Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary clearance disorder, characterized by chronic airway disease. Here, the authors identify mutations in the Multicilin gene, MCIDAS, and suggest that these mutations cause RGMC through disruption of multiciliated cell differentiation.
- Mieke Boon
- , Julia Wallmeier
- & Heymut Omran
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Learning-induced and stathmin-dependent changes in microtubule stability are critical for memory and disrupted in ageing
The microtubule-associated protein stathmin is implicated in cognitive processing but it is unclear how. Here, the authors show that stathmin regulates microtubule stability and dendritic transport of specific AMPA receptor subunits, and that this regulation is impaired in aged mice.
- Shusaku Uchida
- , Guillaume Martel
- & Gleb P. Shumyatsky
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Ciliopathy-associated gene Cc2d2a promotes assembly of subdistal appendages on the mother centriole during cilia biogenesis
Mutations in the centrosome-cilia gene, Cc2d2a, result in Meckel and Joubert syndromes in humans. By creating Cc2d2a-mutant mice, Veleri et al.show that this gene encodes a component of subdistal appendages; ciliary structures thought to be required to anchor cilia to the microtubule network.
- Shobi Veleri
- , Souparnika H. Manjunath
- & Anand Swaroop
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Receptor tyrosine kinase c-Met controls the cytoskeleton from different endosomes via different pathways
The receptor tyrosine kinase c-Met continues to signal following its internalization, recruiting the small GTPase Rac to stimulate cell migration. Ménard et al.show that this Rac signalling results in distinct outcomes depending on the nature of the endosome in which the receptor resides.
- Ludovic Ménard
- , Peter J. Parker
- & Stéphanie Kermorgant
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AmotL2 links VE-cadherin to contractile actin fibres necessary for aortic lumen expansion
Cell–cell adhesion molecules and the cytoskeleton determine endothelial cell shape during the formation of blood vessels. Here the authors show that the scaffold protein, amotL2, couples adherens junctions to contractile cytoskeletal proteins to coordinate cellular morphogenesis with aortic lumen expansion.
- Sara Hultin
- , Yujuan Zheng
- & Lars Holmgren
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APC/C is an essential regulator of centrosome clustering
Cells with multiple centrosomes, as are often observed in cancer, can still divide successfully because the centrosomes cluster to form a single spindle pole body. Drosopoulos et al.show that degradation of the kinesin Eg5 by APC/C-CDH1 is required for centrosome clustering.
- Konstantinos Drosopoulos
- , Chan Tang
- & Spiros Linardopoulos
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Catch-bond behaviour facilitates membrane tubulation by non-processive myosin 1b
The non-processive motor protein myosin 1b is required for Golgi membrane tubulation. Using a minimal reconstituted system and theoretical analysis, Yamada et al.demonstrate that the mechanism of tubule extraction depends on the catch bond properties of myosin 1b.
- Ayako Yamada
- , Alexandre Mamane
- & Patricia Bassereau
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| Open AccessDido3-dependent HDAC6 targeting controls cilium size
Although factors regulating the assembly and disassembly of primary cilia have been identified, mechanisms controlling the steady-state length of the cilium remain poorly understood. Here, the authors show that Dido3 regulates cilium length by mediating the actin-dependent delivery of HDAC6 to the basal body.
- Ainhoa Sánchez de Diego
- , Astrid Alonso Guerrero
- & Karel H. M. van Wely
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MYPT1 regulates contractility and microtubule acetylation to modulate integrin adhesions and matrix assembly
Regulation of adhesion during cell migration requires coordinated control of both microtubule acetylation and actomyosin-dependent contractility. Joo and Yamada show that these systems are reciprocally regulated by myosin phosphatase through its interactions with HDAC6 and myosin light chain respectively.
- E. Emily Joo
- & Kenneth M. Yamada
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Microtubule acetylation amplifies p38 kinase signalling and anti-inflammatory IL-10 production
α-tubulin acetylation is an evolutionarily conserved modification but despite its prevalence, the physiological function of this process remains poorly understood. Here, the authors show that α-tubulin acetylation regulates p38 kinase signalling and expression of the anti-inflammatory cytokine IL-10 in macrophages.
- Bin Wang
- , Yan-Hua Rao
- & Tso-Pang Yao
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| Open AccessSILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale
Actin-dependent motility is driven by the rapid changes in the recruitment of many different structural and regulatory proteins at the cell’s cortex. Sobczyk et al. characterize these changes in the cytoskeletal proteome on a second to minute timescale during chemotactic response in Dictyosteliumusing SILAC-based proteomics.
- Grzegorz J. Sobczyk
- , Jun Wang
- & Cornelis J. Weijer
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Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation
Adipocyte differentiation is accompanied by large scale changes in the actin cytoskeleton. Here, Nobusue et al.show that binding to G-actin sequesters the transcriptional coactivator MKL1 in the cytoplasm, and triggers differentiation by inducing the expression of pro-adipogenic transcription factor PPARγ.
- Hiroyuki Nobusue
- , Nobuyuki Onishi
- & Koichiro Kano
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Structural analysis of the transitional state of Arp2/3 complex activation by two actin-bound WCAs
The involvement of one or two nucleation-promoting factors in Arp2/3 complex activation is a matter of debate. Here Boczkowska et al.provide evidence that two nucleation-promoting factors are required, and propose a model of the 11-subunit transitional complex based on distance measurements by FRET.
- Malgorzata Boczkowska
- , Grzegorz Rebowski
- & Roberto Dominguez
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The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation
On mitotic exit, the nucleoporin MEL-28 binds to chromatin and seeds the formation of nuclear pore complexes. Here Yokoyama et al.show that upon mitotic entry, MEL-28 re-localizes to microtubules where it functions in assembling the mitotic spindle, revealing roles for MEL-28 throughout the cell cycle.
- Hideki Yokoyama
- , Birgit Koch
- & Oliver J. Gruss
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| Open AccessEctopic A-lattice seams destabilize microtubules
Microtubules are tubes in which helical symmetry is broken at a single ‘A-lattice’ seam. Katsuki et al.show that microtubules containing additional A-lattice seams exhibit decreased stability, and propose that such seams may act as trigger points for microtubule catastrophe.
- Miho Katsuki
- , Douglas R. Drummond
- & Robert A. Cross
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| Open AccessActomyosin-dependent formation of the mechanosensitive talin–vinculin complex reinforces actin anchoring
The interaction between focal adhesion proteins vinculin and talin is stimulated by mechanical stretching. Here the authors reconstitute actomyosin-dependent stretching of talin in vitro, and show that the resulting activation of vinculin reinforces anchoring of the adhesion complex to actin.
- Corina Ciobanasu
- , Bruno Faivre
- & Christophe Le Clainche
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| Open AccessGuidance of subcellular tubulogenesis by actin under the control of a synaptotagmin-like protein and Moesin
The terminal branches of the Drosophilatracheal network have intracellular tubules that grow through elongation of membrane invaginations. Here, the authors identify the synaptotagmin-like protein Bitesize as a regulator of actin-dependent luminal membrane morphogenesis.
- N. JayaNandanan
- , Renjith Mathew
- & Maria Leptin
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| Open AccessStructural basis for microtubule recognition by the human kinetochore Ska complex
Kinetochores must interact with both polymerizing (straight) and depolymerizing (curved) microtubules to ensure correct mitotic chromosome segregation. Abad et al. reveal how this flexibility is achieved through structural characterization of the interactions between microtubules and the kinetochore protein Ska1.
- Maria Alba Abad
- , Bethan Medina
- & A. Arockia Jeyaprakash
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Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics
Nck1/2 adaptor proteins control the assembly and activity of protein complexes that promote actin polymerization. Buvall et al.show that Nck1 abundance is regulated by the E3 ubiquitin ligase c-Cbl, which competes for Nck binding with the actin-binding protein synaptopodin in podocytes.
- Lisa Buvall
- , Priyanka Rashmi
- & Peter Mundel
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Transition fibre protein FBF1 is required for the ciliary entry of assembled intraflagellar transport complexes
The primary cilium is a protected cellular niche; however, the mechanisms that control the entry of proteins into this environment are poorly understood. Wei et al.show that FBF1 is a component of transition fibres at the ciliary base, and is required for the entry of intraflagellar transport complexes.
- Qing Wei
- , Qingwen Xu
- & Jinghua Hu
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| Open AccessSeptins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation
Septins are a family of heteropolymerizing GTP/GDP-binding proteins and are implicated in neuritogenesis in nematodes. Ageta-Ishihara et al.show that septins also facilitate this process in the developing mouse brain as scaffolds that coordinate HDAC6-mediated deacetylation of microtubules.
- Natsumi Ageta-Ishihara
- , Takaki Miyata
- & Makoto Kinoshita
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The unusual dynamics of parasite actin result from isodesmic polymerization
Actin normally polymerizes into filaments in a cooperative manner, with nucleation and elongation phases. Skillman et al. show that actin from the protozoan parasite Toxoplasma gondiipolymerizes in an isodesmic manner, without any evidence of nucleation, resulting in filaments that are very short and unstable.
- Kristen M. Skillman
- , Christopher I. Ma
- & L. David Sibley
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Synthetic polyamines promote rapid lamellipodial growth by regulating actin dynamics
While small molecules that destabilize actin filaments are readily available, artificially stimulating actin polymerization in cells typically involves genetic manipulation. Here, the authors design cell-permeable branched polyamines that promote lamellipodium formation by stimulating actin polymerization.
- Iliana Nedeva
- , Girish Koripelly
- & Daniel Riveline
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| Open AccessRab6a releases LIS1 from a dynein idling complex and activates dynein for retrograde movement
LIS1 has been shown to act as a protein ‘clutch’, which binds to dynein motor proteins and prevents microtubule detachment without affecting their ATPase activity; this causes dynein to stall. Here the authors show that the GTPase Rab6a releases LIS1 from dynein, thus reactivating the motor.
- Masami Yamada
- , Kanako Kumamoto
- & Shinji Hirotsune
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| Open AccessMechanism of microtubule array expansion in the cytokinetic phragmoplast
Plant cell division is driven by the expansion of the phragmoplast, a characteristic structure that forms in the middle of the plant cell during cytokinesis. Murata et al. use genetic and cell imaging approaches to clarify the microtubule behaviour that leads to phragmoplast expansion.
- Takashi Murata
- , Toshio Sano
- & Mitsuyasu Hasebe
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αTAT1 is the major α-tubulin acetyltransferase in mice
Acetylation of tubulin is proposed to be an important mechanism for the regulation of microtubule stability and diversity. Kalebic et al. generate mice lacking α-tubulin acetyltransferase activity, and reveal that an apparent absence of detectable tubulin acetylation is associated with impaired sperm motility.
- Nereo Kalebic
- , Simona Sorrentino
- & Paul A. Heppenstall
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Formin mDia1 senses and generates mechanical forces on actin filaments
Formins are a family of protein complexes that accelerate actin filament nucleation and elongation. Jegou et al.show that the formin mDia1 can generate mechanical tension in actin filaments, while conversely, pulling forces applied by viscous drag increase formin elongation activity.
- Antoine Jégou
- , Marie-France Carlier
- & Guillaume Romet-Lemonne
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| Open AccessALKBH4-dependent demethylation of actin regulates actomyosin dynamics
The division of a single eukaryotic cell into two requires actomyosin-dependent contraction. Here the authors show that lysine methylation of actin inhibits contractility during cytokinesis by blocking its association with myosin, and this modification is reversed at the contractile ring by the demethylase ALKBH4.
- Ming-Ming Li
- , Anja Nilsen
- & Yun-Gui Yang
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SAPK pathways and p53 cooperatively regulate PLK4 activity and centrosome integrity under stress
Centrosome duplication during cell division is controlled by the polo-like kinase PLK4. Nakamura et al. reveal how stress-activated protein kinase and the tumour suppressor p53 act together to regulate PLK4, and show that their combined loss in cancer cells leads to the appearance of supernumerary centrosomes.
- Takanori Nakamura
- , Haruo Saito
- & Mutsuhiro Takekawa
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Dual role of myosin II during Drosophila imaginal disc metamorphosis
The motor protein myosin II is implicated in three-dimensional organ development. In this study, the authors apply live imaging techniques to describe the dynamics of the developing Drosophilawing and the involvement of myosin II in this process.
- Silvia Aldaz
- , Luis M. Escudero
- & Matthew Freeman
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| Open AccessThe four-transmembrane protein IP39 of Euglena forms strands by a trimeric unit repeat
IP39 is an abundant protozoan protein known to form highly-ordered striations in Euglena gracilis’ plasma membrane. Here, Suzuki et al. determine its three-dimensional structure by electron crystallography revealing that IP39 polymerises to form trimeric longitudinal units arranged in a molecular strand of antiparallel double-rows.
- Hiroshi Suzuki
- , Yasuyuki Ito
- & Sachiko Tsukita
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| Open AccessRnd3 coordinates early steps of cortical neurogenesis through actin-dependent and -independent mechanisms
The atypical RhoGTPase Rnd3 is implicated in the regulation of neuronal migration in the embryonic cerebral cortex. Using gene silencing techniques, Pacary and colleagues find that Rnd3 is also involved in earlier stages of neurogenesis, by modulating actin filament polymerization and cyclin D1 translation.
- Emilie Pacary
- , Roberta Azzarelli
- & François Guillemot
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N-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways
Cells often migrate in groups, requiring delicate coordination of adhesion between members of the group and between the group and its surroundings. Here the authors show that this distinction is underpinned by differential N-cadherin signalling through p120catenin and β-catenin.
- Mingxing Ouyang
- , Shaoying Lu
- & Yingxiao Wang