Cell Adhesion, Polarity & Cytoskeleton
- 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
- Tyrosination of α‐tubulin controls the initiation of processive dynein–dynactin motility
- 1Department of Cellular and Molecular Pharmacology, the Howard Hughes Medical Institute University of California, San Francisco, CA, USA
- 2Department of Molecular and Cellular Biology, University of California, Davis, CA, USA
- 3 Institute for Stem Cell Biology and Regenerative Medicine, NCBS‐TIFR, Bangalore, India
- ↵*Corresponding author. Tel: +91 80 2366 6630; E‐mail: minhaj{at}instem.res.in
Post‐translational modifications of tubulin can affect motor protein behavior on microtubules. This study reveals that microtubule tyrosination allows for robust initiation of mammalian dynein–dynactin processivity, but that tyrosination is dispensable once dynein is motile.
Synopsis
Post‐translational modifications of tubulin can affect motor protein behavior on microtubules. This study reveals that microtubule tyrosination allows for robust initiation of mammalian dynein–dynactin processivity, but that tyrosination is dispensable once dynein is motile.
Removal of alpha‐tubulin carboxy‐terminal tyrosine strongly decreases the interaction of the dynein–dynactin complex with microtubules.
The dynein–dynactin complex has two separate microtubule binding domains.
The CAP‐Gly domain within the dynactin complex senses the tyrosination state of the microtubule and aids in the initiation of processive dynein motility.
After the initiation of processive motility, the CAP‐Gly interaction with the microtubule is not required for sustained dynein motility.
The EMBO Journal (2016) 35: 1175–1185
- Received September 14, 2015.
- Revision received February 18, 2016.
- Accepted February 18, 2016.
- © 2016 The Authors
- GEMC1 is a critical regulator of multiciliated cell differentiation
- Berta Terré1,†,
- Gabriele Piergiovanni2,†,
- Sandra Segura‐Bayona1,
- Gabriel Gil‐Gómez3,
- Sameh A Youssef4,
- Camille Stephan‐Otto Attolini1,
- Michaela Wilsch‐Bräuninger5,
- Carole Jung6,
- Ana M Rojas7,
- Marko Marjanović1,8,
- Philip A Knobel1,
- Lluís Palenzuela1,
- Teresa López‐Rovira1,
- Stephen Forrow1,
- Wieland B Huttner5,
- Miguel A Valverde6,
- Alain de Bruin4,9,
- Vincenzo Costanzo*,2 and
- Travis H Stracker*,1
- 1Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
- 2FIRC Institute of Molecular Oncology, Milan, Italy
- 3IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain
- 4Dutch Molecular Pathology Center, Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
- 5Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
- 6Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
- 7Computational Biology and Bioinformatics Group, Institute of Biomedicine of Seville, Campus Hospital Universitario Virgen del Rocio, Seville, Spain
- 8Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia
- 9Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
- ↵*
Corresponding author. Tel: +39 2 574303875; E‐mail: vincenzo.costanzo{at}ifom.eu
Corresponding author. Tel: +34 93 4031183; E‐mail: travis.stracker{at}irbbarcelona.org
↵† These authors contributed equally to this study
In addition to a role in DNA replicaion, Geminin‐like coiled‐coil containing protein 1 (GEMC1) interacts with E2F4/5‐DP1 and Multicilin to control transcriptional programs required for multiciliated cell (MCC) differentiation in mammals.
Synopsis
In addition to a role in DNA replicaion, Geminin‐like coiled‐coil containing protein 1 (GEMC1) interacts with E2F4/5‐DP1 and Multicilin to control transcriptional programs required for multiciliated cell (MCC) differentiation in mammals.
GEMC1 is required for normal growth and fertility in mice.
Multiciliated cells and sperm require GEMC1.
GEMC1 interacts with E2F4/5‐DP1 and Multicilin.
Multiciliated cells transcriptional programs are activated by GEMC1.
GEMC1 is a candidate gene for human ciliopathies.
The EMBO Journal (2016) 35: 942–960
- Received August 12, 2015.
- Revision received February 2, 2016.
- Accepted February 5, 2016.
- © 2016 The Authors
- CPAP promotes timely cilium disassembly to maintain neural progenitor pool
- Elke Gabriel1,
- Arpit Wason1,
- Anand Ramani1,
- Li Ming Gooi1,
- Patrick Keller2,
- Andrei Pozniakovsky2,
- Ina Poser2,
- Florian Noack3,
- Narasimha Swamy Telugu4,
- Federico Calegari3,
- Tomo Šarić4,
- Jürgen Hescheler4,
- Anthony A Hyman2,
- Marco Gottardo5,
- Giuliano Callaini5,
- Fowzan Sami Alkuraya6,7 and
- Jay Gopalakrishnan*,1
- 1Center for Molecular Medicine and Institute for Biochemistry I of the University of Cologne, Cologne, Germany
- 2Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany
- 3DFG‐Research Center and Cluster of Excellence for Regenerative Therapies, TU‐Dresden, Dresden, Germany
- 4Center for Physiology and Pathophysiology, Institute for Neurophysiology Medical Faculty University of Cologne, Cologne, Germany
- 5Department of Life Sciences, University of Siena, Siena, Italy
- 6Department of Genetics, King Faisal Specialist Hospital and Research Center Alfasial University, Riyadh, Saudi Arabia
- 7Department of Anatomy and Cell Biology, College of Medicine Alfasial University, Riyadh, Saudi Arabia
- ↵*Corresponding author. Tel: +49 221 478 89691; E‐mail: jay.gopalakrishnan{at}uni-koeln.de
Mutations in centrosomal‐P4.1‐associated protein (CPAP) cause Seckel syndrome. CPAP defects prevent proper cilium disassembly in neural progenitor cells with cell cycle progression delay and premature differentiation, leading to the microcephaly associated with this syndrome.
Synopsis
Mutations in centrosomal‐P4.1‐associated protein (CPAP) cause Seckel syndrome. CPAP defects prevent proper cilium disassembly in neural progenitor cells with cell cycle progression delay and premature differentiation, leading to the microcephaly associated with this syndrome.
In wild‐type NPCs, CPAP‐mediated CDC recruitment allows timely cilium disassembly and normal G1‐S transition.
This enables WT NPCs to undergo symmetric proliferation and NPC pool expansion.
In failure of efficient CPAP‐mediated CDC recruitment, Seckel NPCs exhibit a retarded cilium disassembly and an extended G1‐S transition (extended red arrow).
This triggers premature NPC differentiation leading to NPC loss and microcephaly.
The EMBO Journal (2016) 35: 803–819
- Received December 11, 2015.
- Revision received February 2, 2016.
- Accepted February 5, 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.
- Intraflagellar transport proteins 172, 80, 57, 54, 38, and 20 form a stable tubulin‐binding IFT‐B2 complex
- Michael Taschner1,†,
- Kristina Weber1,†,
- André Mourão1,
- Melanie Vetter1,
- Mayanka Awasthi1,
- Marc Stiegler1,
- Sagar Bhogaraju1 and
- Esben Lorentzen*,1
- ↵*Corresponding author. Tel: +49 89 8578 3479; Fax: +49 89 8578 3605; E‐mail: lorentze{at}biochem.mpg.de
↵† These authors contributed equally to this work
Thought to be peripheral components of the IFT‐B complex, IFT172, 80, 57, 54, and 20 form a stable sub‐complex (IFT‐B2). IFT‐B2 interacts with tubulin/microtubules and connects them to the core IFT‐B1 complex through interaction with IFT88/52.
Synopsis
Thought to be peripheral components of the IFT‐B complex, IFT172, 80, 57, 54, and 20 form a stable sub‐complex (IFT‐B2). IFT‐B2 interacts with tubulin/microtubules and connects them to the core IFT‐B1 complex through interaction with IFT88/52.
Peripheral IFT‐B complex proteins IFT172, 80, 57, 54, and 20 form a stable IFT‐B2 complex that we reconstitute and purify.
IFT‐B2 interacts with the IFT‐B1 (core) complex via IFT88/52 to form the full IFT‐B complex.
IFT‐B2 binds tubulin/MT via the N‐terminal calponin homology (CH) domain of IFT54.
High‐resolution crystal structures of IFT52N and IFT54N reveal residues critical to IFT‐B complex assembly and tubulin binding.
The EMBO Journal (2016) 35: 773–790
- Received September 29, 2015.
- Revision received January 15, 2016.
- Accepted January 21, 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.
- Microtubule‐binding protein doublecortin‐like kinase 1 (DCLK1) guides kinesin‐3‐mediated cargo transport to dendrites
- 1Cell Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands
- 2Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Warsaw, Poland
- ↵*Corresponding author. Tel: +31 30 2533894; Fax: +31 30 2513655; E‐mail: c.hoogenraad{at}uu.nl
While kinesin motors selectively move into axons, kinesin‐3 and kinesin‐4 can also target dendrites. Microtubule‐binding protein doublecortin‐like kinase 1 (DCLK1) provides local cues to steer polarized movement of kinesin‐3 into dendrites.
Synopsis
While kinesin motors selectively move into axons, kinesin‐3 and kinesin‐4 can also target dendrites. Microtubule‐binding protein doublecortin‐like kinase 1 (DCLK1) provides local cues to steer polarized movement of kinesin‐3 into dendrites.
Twenty‐three members of the kinesin subfamily are able to transport cargo in living cells.
Kinesin‐3 (KIF1) and kinesin‐4 (KIF21) family members target both axon and dendrites.
DCLK1 associates with a specific subset of microtubules in dendrites.
DCLK1 is required for KIF1‐mediated dense‐core vesicle trafficking into dendrites.
The EMBO Journal (2016) 35: 302–318
- Received August 26, 2015.
- Revision received December 2, 2015.
- Accepted December 8, 2015.
- © 2016 The Authors
- Eradicating tumor drug resistance at its YAP‐biomechanical roots
Treatment with BRAF kinase inhibitors leads to rapid resistance and tumor regression in BRAF V600E mutant melanoma patients. However, the underlying mechanism of the developed tumor resistance is not fully clear. In this issue of The EMBO Journal, Kim and colleagues show that melanoma cells acquire resistance to BRAF inhibitors by changing cell shape, modifying their cytoskeleton and, in turn, activating the YAP/TAZ mechanotransduction pathway (Kim et al, 2016).
See also: MH Kim et al (March 2016)
New findings report that melanoma cells acquire resistance to BRAF inhibitors by changing cell shape, modifying their cytoskeleton and, in turn, activating the YAP/TAZ mechanotransduction pathway.
- © 2015 The Authors
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