Cell Adhesion, Polarity & Cytoskeleton
- Hippo kinases maintain polarity during directional cell migration in Caenorhabditis elegans
- Guoxin Feng1,
- Zhiwen Zhu1,
- Wen‐Jun Li2,
- Qirong Lin1,
- Yongping Chai1,
- Meng‐Qiu Dong2 and
- Guangshuo Ou (guangshuoou{at}tsinghua.edu.cn)*,1
- 1Tsinghua‐Peking Center for Life Sciences, School of Life Sciences and MOE Key Laboratory for Protein Science, Tsinghua University, Beijing, China
- 2National Institute of Biological Science, Beijing, China
- ↵*Corresponding author. Tel: +86 10 62794766; E‐mail: guangshuoou{at}tsinghua.edu.cn
The anterior–posterior migration of neuroblast progeny in C. elegans larvae is regulated by the interplay between Hippo kinases and Rho GTPase MIG‐2 activity.
Synopsis
Directional cell migration in C. elegans requires reciprocal regulation between Hippo kinases and Rho GTPase MIG‐2 to ensure correct positioning of neural progenitors.
Hippo kinases are crucial for directional cell migration in C. elegans.
Hippo kinases maintain the anterior–posterior directional cell migration by inhibiting the ectopic dorsal–ventral migration.
Hippo kinases directly phosphorylate C. elegans Rho GTPase MIG‐2 on a conserved serine 139.
MIG‐2S139 phosphorylation impedes actin assembly in migrating cells.
Hippo kinases are excluded from the leading edge by MIG‐2‐mediated polarization.
The EMBO Journal (2017) 36: 334–345
- Received September 14, 2016.
- Revision received November 7, 2016.
- Accepted November 16, 2016.
- © 2016 The Authors
- SHARPIN regulates collagen architecture and ductal outgrowth in the developing mouse mammary gland
- Emilia Peuhu (emilia.peuhu{at}utu.fi)*,1,
- Riina Kaukonen1,†,
- Martina Lerche1,†,
- Markku Saari1,
- Camilo Guzmán1,
- Pia Rantakari2,3,
- Nicola De Franceschi1,
- Anni Wärri1,
- Maria Georgiadou1,
- Guillaume Jacquemet1,
- Elina Mattila1,
- Reetta Virtakoivu1,
- Yuming Liu4,
- Youmna Attieh5,
- Kathleen A Silva6,
- Timo Betz5,7,
- John P Sundberg6,
- Marko Salmi2,3,
- Marie‐Ange Deugnier5,8,
- Kevin W Eliceiri4 and
- Johanna Ivaska (johanna.ivaska{at}utu.fi)*,1,9
- 1Centre for Biotechnology, University of Turku, Turku, Finland
- 2MediCity Research Laboratory, University of Turku, Turku, Finland
- 3Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland
- 4Department of Biomedical Engineering, Laboratory for Optical and Computational Instrumentation (LOCI), University of Wisconsin at Madison, Madison, WI, USA
- 5Institut Curie, Paris Sciences et Lettres Research University, Paris, France
- 6The Jackson Laboratory, Bar Harbor, ME, USA
- 7Center for Molecular Biology of Inflammation, Cells‐in‐Motion Cluster of Excellence, Institute of Cell Biology, Münster University, Münster, Germany
- 8Institut Curie, CNRS, UMR144, Paris, France
- 9Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland
- ↵*
Corresponding author. Tel: +358 2 333 7953; E‐mail: emilia.peuhu{at}utu.fi
Corresponding author. Tel: +358 2 333 7954; E‐mail: johanna.ivaska{at}utu.fi
↵† These authors contributed equally to this work
Adhesion regulator SHARPIN modulates stromal collagen architecture and matrix turnover in mammary gland fibroblasts during puberty and thereby regulates the outgrowth of mammary ducts.
Synopsis
SHARPIN is implicated in regulation of extracellular matrix adhesion molecules. New data show that SHARPIN modulates stromal collagen architecture and matrix turnover in mammary gland fibroblasts during puberty and thereby regulates the outgrowth of mammary ducts.
Mice lacking SHARPIN expression (Sharpincpdm) have reduced mammary ductal outgrowth during puberty.
Transplantation studies and conditional knockouts show that stromal, and not epithelial, SHARPIN regulates mammary gland development.
Collagen bundling and extracellular matrix stiffness are reduced in the Sharpincpdm mammary gland stroma.
Mammary gland fibroblasts that lack SHARPIN demonstrate defective collagen remodelling and turnover in vitro.
The EMBO Journal (2017) 36: 165–182
- Received March 21, 2016.
- Revision received October 28, 2016.
- Accepted October 28, 2016.
- © 2016 The Authors
- Endothelial basement membrane laminin 511 is essential for shear stress response
- Jacopo Di Russo1,2,
- Anna‐Liisa Luik1,2,
- Lema Yousif1,2,
- Sigmund Budny1,2,
- Hans Oberleithner2,3,
- Verena Hofschröer2,3,
- Juergen Klingauf2,4,
- Ed van Bavel5,
- Erik NTP Bakker5,
- Per Hellstrand6,
- Anirban Bhattachariya6,
- Sebastian Albinsson6,
- Frederic Pincet7,8,
- Rupert Hallmann1,2 and
- Lydia M Sorokin (sorokin{at}uni-muenster.de)*,1,2
- 1Institute of Physiological Chemistry and Pathobiochemistry, University of Muenster, Muenster, Germany
- 2Cells‐in‐Motion Cluster of Excellence, University of Muenster, Muenster, Germany
- 3Institute of Physiology II, University of Muenster, Muenster, Germany
- 4Institute of Medical Physics, University of Muenster, Muenster, Germany
- 5Biomedical Engineering and Physics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
- 6Department of Experimental Medical Science, Lund University, Lund, Sweden
- 7Laboratoire de Physique Statistique, École Normale Superieure – PSL Research University, Paris, France
- 8CNRS UMR8550, Sorbonne Universités − UPMC Univ Paris 06, Université Paris, Paris, France
- ↵*Corresponding author. Tel: +49 251 8355581; Fax: +49 251 83 55596; E‐mail: sorokin{at}uni-muenster.de
Laminin 511 (Laminin α5) is required for adhesion of endothelial cells to their basement membrane and stabilizes junctional VE‐cadherin, and this is required for the shear stress response of resistance arteries.
Synopsis
Laminin 511 (Laminin α5) is required for adhesion of endothelial cells to their basement membrane and stabilizes junctional VE‐cadherin, and this is required for the shear stress response of resistance arteries.
Laminin 511 is crucial for physiological endothelial cell shear stress‐induced arterial vasodilation.
Integrin β1‐mediated adhesion of arterial endothelial cells to laminin 511 stabilizes VE‐cadherin at adherens junctions.
Laminin 511 regulates endothelial cell actin cortical tension in vivo.
The EMBO Journal (2017) 36: 183–201
- Received May 11, 2016.
- Revision received November 8, 2016.
- Accepted November 9, 2016.
- © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- Stabilization of the metaphase spindle by Cdc14 is required for recombinational DNA repair
- María Teresa Villoria1,†,
- Facundo Ramos1,†,
- Encarnación Dueñas1,
- Peter Faull2,
- Pedro Rodríguez Cutillas2,3 and
- Andrés Clemente‐Blanco (andresclemente{at}usal.es)*,1
- 1Cell Cycle and Genome Stability Group, Instituto de Biología Funcional y Genómica Consejo Superior de Investigaciones Científicas (CSIC) Universidad de Salamanca (USAL), Salamanca, Spain
- 2Biological Mass Spectrometry and Proteomics Laboratory, Medical Research Council Clinical Science Centre Imperial College, London, UK
- 3Integrative Cell Signalling and Proteomics Group, Centre for Haemato‐Oncology Barts Cancer Institute John Vane Science Centre Queen Mary University of London, London, UK
- ↵*Corresponding author. Tel: +34 923 294 887; E‐mail: andresclemente{at}usal.es
↵† These authors contributed equally to this work
Dephosphorylation of yeast Spc110 by Cdc14 helps to stabilize mitotic spindles and promotes recruitment of damaged DNA to spindle pole bodies for efficient repair.
Synopsis
In yeast, DNA damage causes re‐localization of DNA breaks to the nuclear periphery for efficient repair. New work implicates the Cdk‐counteracting phosphatase Cdc14 in promoting spindle‐dependent recruitment of DNA lesions to spindle pole bodies.
Cdc14 is partially released from the nucleolus into the nucleoplasm upon DNA damage.
Cdc14‐dependent Spc110 dephosphorylation contributes to stabilization of the metaphase spindle.
Spindle integrity is important to stimulate the tethering of DNA lesions to the spindle pole bodies.
Recruitment of DNA breaks to spindle pole bodies enhances their repair by homologous recombination.
The EMBO Journal (2017) 36: 79–101
- Received November 20, 2015.
- Revision received October 5, 2016.
- Accepted October 18, 2016.
- © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- MicroRNA‐34/449 controls mitotic spindle orientation during mammalian cortex development
- Juan Pablo Fededa (jpfededa{at}gmail.com)*,1,
- Christopher Esk1,
- Beata Mierzwa1,
- Rugile Stanyte1,
- Shuiqiao Yuan2,
- Huili Zheng2,
- Klaus Ebnet3,
- Wei Yan2,
- Juergen A Knoblich1 and
- Daniel W Gerlich (daniel.gerlich{at}imba.oeaw.ac.at)*,1
- 1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) Vienna Biocenter (VBC), Vienna, Austria
- 2Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV, USA
- 3Institute‐associated Research Group “Cell Adhesion and Cell Polarity”, Institute of Medical Biochemistry, ZMBE, Münster, Germany
- ↵*
Corresponding author. Tel: +43 1 7904 44762; E‐mail: jpfededa{at}gmail.com
Corresponding author. Tel: +43 1 7904 44760; E‐mail: daniel.gerlich{at}imba.oeaw.ac.at
A high‐throughput imaging screen identifies a set of miRNAs that control mitotic spindle orientation in neuronal progenitors and radial glial cells and whose expression is required for normal cortical development in mouse.
Synopsis
A high‐throughput imaging screen identifies a set of miRNAs that control mitotic spindle orientation in neuronal progenitors and radial glial cells and whose expression is required for normal cortical development in mouse.
An in vitro screen identified miR‐34/449 as a candidate cortical miRNA involved in mitotic spindle orientation.
miR‐34/449 is required for normal neurogenesis during mouse cortical development.
The production of neurogenic intermediate progenitors depends on miR‐34/449, which controls mitotic spindle orientation in radial glial cells.
miR‐34/449 regulates spindle orientation at least in part by directly targeting and inhibiting JAM‐A.
The EMBO Journal (2016) 35: 2386–2398
- Received February 5, 2016.
- Revision received August 18, 2016.
- Accepted September 6, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Quantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging
- Manuel Bauer1,2,†,
- Fabien Cubizolles1,†,
- Alexander Schmidt1 and
- Erich A Nigg (erich.nigg{at}unibas.ch)*,1
- ↵*Corresponding author. Tel: +41 61 267 16 56; E‐mail: erich.nigg{at}unibas.ch
↵† These authors contributed equally to this work
A combination of quantitative approaches allows to estimate the absolute and relative abundance of key centrosomal and centriolar proteins in human cells.
Synopsis
Constituents and assembly of centrosomes have been well studied, but quantitative information on the abundance of their components is needed to fully understand the pathophysiological consequences of structural and numerical centrosome aberrations. Here, a combination of approaches estimates the abundance of key centrosomal proteins in human cells.
Quantitative estimates are based on a combination of targeted proteomics and fluorescence imaging.
Quantitative information is provided for whole‐cell lysates and for isolated centrosomes.
We predict 1 STIL molecule for every Sas‐6 dimer at centrioles.
We estimate that cartwheel structures of human centrioles harbor up to 16 stacked hubs.
The EMBO Journal (2016) 35: 2152–2166
- Received April 1, 2016.
- Revision received July 22, 2016.
- Accepted July 25, 2016.
- © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- Phosphorylation‐dependent Akt–Inversin interaction at the basal body of primary cilia
- Futoshi Suizu1,
- Noriyuki Hirata1,
- Kohki Kimura1,
- Tatsuma Edamura1,
- Tsutomu Tanaka1,
- Satoko Ishigaki1,
- Thoria Donia2,
- Hiroko Noguchi3,
- Toshihiko Iwanaga4 and
- Masayuki Noguchi*,1
- 1Division of Cancer Biology, Institute for Genetic Medicine Hokkaido University, Sapporo, Japan
- 2Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt
- 3Department of Pathology, Teine Keijinkai Hospital, Sapporo, Japan
- 4Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
- ↵*Corresponding author. Tel: +81 11 706 5069; Fax: +81 11 706 7826; E‐mail: m_noguch{at}igm.hokudai.ac.jp
Akt–Inversin interplay exemplifies a new Akt role in ciliary physiology, ensuring spindle axis integrity during cell division and kidney development.
Synopsis
Cilia are sensory organelles that play important roles in human kidney development and disease. Mutation of the cilial protein Inversin (INVS) causes autosomal recessive chronic nephropathy (nephronophthisis type II; NPHP2), and accordingly, INVS has been found to associate with nephrocystin 3 (NPHP3) and microtubule cytoskeleton. Here, the kinase Akt is shown to regulate cilia physiology and renal integrity by interaction with the INVS at the basal body.
Akt directly interacts with and phosphorylates INVS.
INVS conserved amino acids 864–866 are required for phosphorylation by Akt, as well as INVS homodimerization.
INVS and p‐Akt co‐localize at the ciliary base centrosome, and recruitment of INVS is stimulated by PDGFRα/Akt signaling.
MDCK cells expressing a mutant INVS that lacks the phosphorylation site 864–866 exhibit impaired ciliogenesis and misalignment of spindle axis during cell division, leading to suppressed cell growth and distorted formation of tubular lumina.
The EMBO Journal (2016) 35: 1346–1363
- Received September 4, 2015.
- Revision received March 4, 2016.
- Accepted April 6, 2016.
- © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
- Rac1‐Rab11‐FIP3 regulatory hub coordinates vesicle traffic with actin remodeling and T‐cell activation
- Jérôme Bouchet*,1,2,3,6,
- Iratxe del Río‐Iñiguez1,2,3,
- Rémi Lasserre1,2,7,
- Sonia Agüera‐Gonzalez1,2,8,
- Céline Cuche1,2,3,
- Anne Danckaert4,
- Mary W McCaffrey5,
- Vincenzo Di Bartolo1,2,3 and
- Andrés Alcover*,1,2,3
- 1Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France
- 2CNRS URA 1961, Paris, France
- 3INSERM U1221, Paris, France
- 4Institut Pasteur Citech‐Imagopole, Paris, France
- 5Molecular Cell Biology Laboratory, Biosciences Institute, School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland
- 6Institut Cochin INSERM, U1016, CNRS, UMR8104, Sorbonne Paris Cité, Université Paris Descartes, Paris, France
- 7Centre d'Immunologie de Marseille Luminy, Université Aix‐Marseille, CNRS UMR7280, INSERM U1104, Marseille, France
- 8Institut Curie, Membrane and Cytoskeleton Dynamics Group, CNRS UMR144, Paris, France
- ↵*
Corresponding author. E‐mail: jerome.bouchet{at}inserm.fr
Corresponding author. E‐mail: andres.alcover{at}pasteur.fr
Rac1‐mediated actin cytoskeleton rearrangements required for normal T‐cell morphology and activation depend on association of Rac1 with Rab11‐FIP3‐positive recycling endosomes.
Synopsis
Rac1‐mediated actin cytoskeleton rearrangements required for normal T‐cell morphology and activation depend on association of Rac1 with Rab11‐FIP3‐positive recycling endosomes.
Rac1 is associated with Rab11‐positive recycling endosomes.
Rab11 and its effector protein FIP3 regulate Rac1 subcellular localization, controlling the equilibrium between membrane and endosome associated Rac1.
FIP3 silencing disperses Rac1 endosomes in the cytoplasm.
Rac1 dispersal leads to altered T‐cell cortical rigidity, T‐cell spreading, and immunological synapse symmetry.
FIP3 silencing leads to increased T‐cell activation and cytokine production in a Rac1‐dependent manner.
The EMBO Journal (2016) 35: 1160–1174
- Received October 14, 2015.
- Revision received March 2, 2016.
- Accepted April 5, 2016.
- © 2016 The Authors
- A tale of two α‐tubulin tails
- Victoria J Allan (viki.allan{at}manchester.ac.uk)1
Post‐translational modifications of tubulin, such as the removal of the C‐terminal tyrosine of α‐tubulin, have long been proposed to influence the ability of microtubule motors to walk along the microtubule surface. This hypothesis has now been tested for cytoplasmic dynein‐1 (dynein), revealing that active dynein–dynactin–adaptor complexes prefer to start moving on tyrosinated microtubules. This choice is governed by the p150 subunit of dynactin. Once moving, however, dynein is not choosy about whether the microtubule is tyrosinated or not.
See also: RJ McKenney et al (June 2016)
Microtubule tyrosination at the C‐terminus of α‐tubulin allows for robust initiation of mammalian dynein‐dynactin processivity, but tyrosination is dispensable once dynein is motile.
- © 2016 The Author
- It's a family act: the geminin triplets take center stage in motile ciliogenesis
The balance between proliferation and differentiation is a fundamental aspect of multicellular life. Perhaps nowhere is this delicate balance more palpable than in the multiciliated cells (MCCs) that line the respiratory tract, the ependyma, and the oviduct. These cells contain dozens to hundreds of motile cilia that beat in a concerted fashion to generate directed fluid flow over the tissue surface. Although MCCs have exited the cell cycle, remarkably, they retain the ability to duplicate their centrioles and to mature those centrioles into ciliary basal bodies—two features, which are known to be normally under strict cell cycle control (Firat‐Karalar & Stearns, 2014). How post‐mitotic MCCs retain this ability, remains unclear. In the past several months, four research articles, including one from Terré et al in this issue of The EMBO Journal, have described a vital role for the geminin coiled‐coil domain‐containing protein (Gemc1) in the MCC gene expression program in multiple tissues and organisms, that bring us closer to understanding this question (Kyrousi et al, 2015; Zhou et al, 2015; Arbi et al, 2016; Terré et al, 2016).
See also: B Terré et al (May 2016) and
M Arbi et al (March 2016)
Multiciliated cells are key components of epithelia in the respiratory tract, the ependyma, and the oviducts. Four recent articles identify a conserved role for GemC1 at the center of a complex gene regulatory network that controls the differentiation of these cells.
- © 2016 The Authors
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