Journal of Molecular Medicine

, Volume 91, Issue 7, pp 803–809 | Cite as

Role of dynamin 2 in the disassembly of focal adhesions

  • Laura Briñas
  • Stéphane Vassilopoulos
  • Gisèle Bonne
  • Pascale Guicheney
  • Marc BitounEmail author


Dynamin 2 (DNM2) is involved in endocytosis and intracellular membrane trafficking through its function in vesicle formation from distinct membrane compartments. During the last decade, several studies pointed out an important role of DNM2-dependent trafficking in turnover of focal adhesions which represent a physical link between the extracellular matrix and the intracellular actin cytoskeleton, and a platform for several signalling pathways. Here, we review the involvement of DNM2 in structural and functional aspects of the focal adhesion sites. Mutations in the DNM2 gene cause two hereditary neuromuscular disorders: dominant centronuclear myopathy and Charcot–Marie–Tooth peripheral neuropathy. Potential impairment of focal adhesions as a pathophysiological hypothesis in DNM2-related human diseases is discussed.


Dynamin 2 Focal adhesion Endocytosis Focal adhesion disassembly 



This work was supported by the Institut National de la Santé et de la Recherche Médicale, the Association Institut de Myologie (AIM), the Université Pierre et Marie Curie-Paris6 and the Centre National de la Recherche Scientifique. LB is recipient of an AIM fellowship.

Conflict of interest

There is no conflict of interest to disclose.


  1. 1.
    Warnock DE, Baba T, Schmid SL (1997) Ubiquitously expressed dynamin-II has a higher intrinsic GTPase activity and a greater propensity for self-assembly than neuronal dynamin-I. Mol Biol Cell 8:2553–2562PubMedGoogle Scholar
  2. 2.
    Gold ES, Underhill DM, Morrissette NS, Guo J, McNiven MA, Aderem A (1999) Dynamin 2 is required for phagocytosis in macrophages. J Exp Med 190:1849–1856PubMedCrossRefGoogle Scholar
  3. 3.
    Henley JR, Krueger EW, Oswald BJ, McNiven MA (1998) Dynamin-mediated internalization of caveolae. J Cell Biol 141:85–99PubMedCrossRefGoogle Scholar
  4. 4.
    van Dam EM, Stoorvogel W (2002) Dynamin-dependent transferrin receptor recycling by endosome-derived clathrin-coated vesicles. Mol Biol Cell 13:169–182PubMedCrossRefGoogle Scholar
  5. 5.
    Jones SM, Howell KE, Henley JR, Cao H, McNiven MA (1998) Role of dynamin in the formation of transport vesicles from the trans-Golgi network. Science 279:573–577PubMedCrossRefGoogle Scholar
  6. 6.
    Tanabe K, Takei K (2009) Dynamic instability of microtubules requires dynamin 2 and is impaired in a Charcot–Marie–Tooth mutant. J Cell Biol 185:939–948PubMedCrossRefGoogle Scholar
  7. 7.
    McNiven MA, Kim L, Krueger EW, Orth JD, Cao H, Wong TW (2000) Regulated interactions between dynamin and the actin-binding protein cortactin modulate cell shape. J Cell Biol 151:187–198PubMedCrossRefGoogle Scholar
  8. 8.
    Mooren OL, Kotova TI, Moore AJ, Schafer DA (2009) Dynamin2 GTPase and cortactin remodel actin filaments. J Biol Chem 284:23995–24005PubMedCrossRefGoogle Scholar
  9. 9.
    Dong J, Misselwitz R, Welfle H, Westermann P (2000) Expression and purification of dynamin II domains and initial studies on structure and function. Protein Expr Purif 20:314–323PubMedCrossRefGoogle Scholar
  10. 10.
    Durieux A, Prudhon B, Guicheney P, Bitoun M (2010) Dynamin 2 and human diseases. J Mol Med 88:339–350PubMedCrossRefGoogle Scholar
  11. 11.
    Zuchner S, Noureddine M, Kennerson M, Verhoeven K, Claeys K, De Jonghe P, Merory J, Oliveira SA, Speer MC, Stenger JE et al (2005) Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot–Marie–Tooth disease. Nat Genet 37:289–294PubMedCrossRefGoogle Scholar
  12. 12.
    Bitoun M, Maugenre S, Jeannet PY, Lacène E, Ferrer X, Laforêt P, Martin JJ, Laporte J, Lochmuller H, Beggs AH et al (2005) Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet 37:1207–1209PubMedCrossRefGoogle Scholar
  13. 13.
    Kanchanawong P, Shtengel G, Pasapera AM, Ramko EB, Davidson MW, Hess HF, Waterman CM (2010) Nanoscale architecture of integrin-based cell adhesions. Nature 468:580–584PubMedCrossRefGoogle Scholar
  14. 14.
    Kharbanda S, Saleem A, Yuan Z, Emoto Y, Prasad KV, Kufe D (1995) Stimulation of human monocytes with macrophage colony-stimulating factor induces a Grb2-mediated association of the focal adhesion kinase pp125FAK and dynamin. Proc Natl Acad Sci U S A 92:6132–6136PubMedCrossRefGoogle Scholar
  15. 15.
    Webb DJ, Donais K, Whitmore LA, Thomas SM, Turner CE, Parsons JT, Horwitz AF (2004) FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol 6:154–161PubMedCrossRefGoogle Scholar
  16. 16.
    Schober M, Raghavan S, Nikolova M, Polak L, Pasolli HA, Beggs HE, Reichardt LF, Fuchs E (2007) Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics. J Cell Biol 176:667–680PubMedCrossRefGoogle Scholar
  17. 17.
    Kaverina I, Krylyshkina O, Small JV (1999) Microtubule targeting of substrate contacts promotes their relaxation and dissociation. J Cell Biol 146:1033–1044PubMedCrossRefGoogle Scholar
  18. 18.
    Ezratty EJ, Partridge MA, Gundersen GG (2005) Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol 7:581–590PubMedCrossRefGoogle Scholar
  19. 19.
    Wang Y, Cao H, Chen J, McNiven MA (2011) A direct interaction between the large GTPase dynamin-2 and FAK regulates focal adhesion dynamics in response to active Src. Mol Biol Cell 22:1529–1538PubMedCrossRefGoogle Scholar
  20. 20.
    Cao H, Chen J, Krueger EW, McNiven MA (2010) SRC-mediated phosphorylation of dynamin and cortactin regulates the “constitutive” endocytosis of transferrin. Mol Cell Biol 30:781–792PubMedCrossRefGoogle Scholar
  21. 21.
    Ezratty EJ, Bertaux C, Marcantonio EE, Gundersen GG (2009) Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells. J Cell Biol 187:733–747PubMedCrossRefGoogle Scholar
  22. 22.
    Chao WT, Kunz J (2009) Focal adhesion disassembly requires clathrin-dependent endocytosis of integrins. FEBS Lett 583:1337–1343PubMedCrossRefGoogle Scholar
  23. 23.
    Chao WT, Ashcroft F, Daquinag AC, Vadakkan T, Wei Z, Zhang P, Dickinson ME, Kunz J (2010) Type I phosphatidylinositol phosphate kinase beta regulates focal adhesion disassembly by promoting beta1 integrin endocytosis. Mol Cell Biol 30:4463–4479PubMedCrossRefGoogle Scholar
  24. 24.
    Vassilieva EV, Gerner-Smidt K, Ivanov AI, Nusrat A (2008) Lipid rafts mediate internalization of beta1-integrin in migrating intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 295:G965–G976PubMedCrossRefGoogle Scholar
  25. 25.
    Bass MD, Williamson RC, Nunan RD, Humphries JD, Byron A, Morgan MR, Martin P, Humphries MJ (2011) A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis. Dev Cell 21:681–693PubMedCrossRefGoogle Scholar
  26. 26.
    Yoo J, Jeong MJ, Cho HJ, Oh ES, Han MY (2005) Dynamin II interacts with syndecan-4, a regulator of focal adhesion and stress-fiber formation. Biochem Biophys Res Commun 328:424–431PubMedCrossRefGoogle Scholar
  27. 27.
    Echtermeyer F, Baciu PC, Saoncella S, Ge Y, Goetinck PF (1999) Syndecan-4 core protein is sufficient for the assembly of focal adhesions and actin stress fibers. J Cell Sci 112:3433–3441PubMedGoogle Scholar
  28. 28.
    Woods A, Longley RL, Tumova S, Couchman JR (2000) Syndecan-4 binding to the high affinity heparin-binding domain of fibronectin drives focal adhesion formation in fibroblasts. Arch Biochem Biophys 374:66–72PubMedCrossRefGoogle Scholar
  29. 29.
    Wilcox-Adelman SA, Denhez F, Goetinck PF (2002) Syndecan-4 modulates focal adhesion kinase phosphorylation. J Biol Chem 277:32970–32977PubMedCrossRefGoogle Scholar
  30. 30.
    Tkachenko E, Lutgens E, Stan RV, Simons M (2004) Fibroblast growth factor 2 endocytosis in endothelial cells proceed via syndecan-4-dependent activation of Rac1 and a Cdc42-dependent macropinocytic pathway. J Cell Sci 117:3189–3199PubMedCrossRefGoogle Scholar
  31. 31.
    Oh ES, Woods A, Lim ST, Theibert AW, Couchman JR (1998) Syndecan-4 proteoglycan cytoplasmic domain and phosphatidylinositol 4,5-bisphosphate coordinately regulate protein kinase C activity. J Biol Chem 273:10624–10629PubMedCrossRefGoogle Scholar
  32. 32.
    Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651–657PubMedCrossRefGoogle Scholar
  33. 33.
    De Deyne PG, O'Neill A, Resneck WG, Dmytrenko GM, Pumplin DW, Bloch RJ (1998) The vitronectin receptor associates with clathrin-coated membrane domains via the cytoplasmic domain of its beta5 subunit. J Cell Sci 111:2729–2740PubMedGoogle Scholar
  34. 34.
    Merisko EM, Welch JK, Chen TY, Chen M (1988) Alpha-actinin and calmodulin interact with distinct sites on the arms of the clathrin trimer. J Biol Chem 263:15705–15712PubMedGoogle Scholar
  35. 35.
    Fausser JL, Ungewickell E, Ruch JV, Lesot H (1993) Interaction of vinculin with the clathrin heavy chain. J Biochem 114:498–503PubMedGoogle Scholar
  36. 36.
    Stehbens S, Wittmann T (2012) Targeting and transport: how microtubules control focal adhesion dynamics. J Cell Biol 198:481–489PubMedCrossRefGoogle Scholar
  37. 37.
    Franco SJ, Rodgers MA, Perrin BJ, Han J, Bennin DA, Critchley DR, Huttenlocher A (2004) Calpain-mediated proteolysis of talin regulates adhesion dynamics. Nat Cell Biol 6:977–983PubMedCrossRefGoogle Scholar
  38. 38.
    Chan KT, Bennin DA, Huttenlocher A (2010) Regulation of adhesion dynamics by calpain-mediated proteolysis of focal adhesion kinase (FAK). J Biol Chem 285:11418–11426PubMedCrossRefGoogle Scholar
  39. 39.
    Burridge K, Sastry SK, Sallee JL (2006) Regulation of cell adhesion by protein-tyrosine phosphatases. I. Cell–matrix adhesion. J Biol Chem 281:15593–15596PubMedCrossRefGoogle Scholar
  40. 40.
    Mitra SK, Hanson DA, Schlaepfer DD (2005) Focal adhesion kinase: in command and control of cell motility. Nat Rev Mol Cell Biol 6:56–68PubMedCrossRefGoogle Scholar
  41. 41.
    Spinardi L, Marchisio PC (2006) Podosomes as smart regulators of cellular adhesion. Eur J Cell Biol 85:191–194PubMedCrossRefGoogle Scholar
  42. 42.
    Bruzzaniti A, Neff L, Sandoval A, Du L, Horne WC, Baron R (2009) Dynamin reduces Pyk2 Y402 phosphorylation and SRC binding in osteoclasts. Mol Cell Biol 29:3644–3656PubMedCrossRefGoogle Scholar
  43. 43.
    Eleniste PP, Du L, Shivanna M, Bruzzaniti A (2012) Dynamin and PTP-PEST cooperatively regulate Pyk2 dephosphorylation in osteoclasts. Int J Biochem Cell Biol 44:790–800PubMedCrossRefGoogle Scholar
  44. 44.
    Shen Y, Lyons P, Cooley M, Davidson D, Veillette A, Salgia R, Griffin JD, Schaller MD (2000) The noncatalytic domain of protein-tyrosine phosphatase-PEST targets paxillin for dephosphorylation in vivo. J Biol Chem 275:1405–1413PubMedCrossRefGoogle Scholar
  45. 45.
    Angers-Loustau A, Cote JF, Charest A, Dowbenko D, Spencer S, Lasky LA, Tremblay ML (1999) Protein tyrosine phosphatase-PEST regulates focal adhesion disassembly, migration, and cytokinesis in fibroblasts. J Cell Biol 144:1019–1031PubMedCrossRefGoogle Scholar
  46. 46.
    Bhatt A, Kaverina I, Otey C, Huttenlocher A (2002) Regulation of focal complex composition and disassembly by the calcium-dependent protease calpain. J Cell Sci 115:3415–3425PubMedGoogle Scholar
  47. 47.
    Schafer DA, Weed SA, Binns D, Karginov AV, Parsons JT, Cooper JA (2002) Dynamin2 and cortactin regulate actin assembly and filament organization. Curr Biol 12:1852–1857PubMedCrossRefGoogle Scholar
  48. 48.
    Itoh T, Erdmann KS, Roux A, Habermann B, Werner H, De Camilli P (2005) Dynamin and the actin cytoskeleton cooperatively regulate plasma membrane invagination by BAR and F-BAR proteins. Dev Cell 9:791–804PubMedCrossRefGoogle Scholar
  49. 49.
    Lee E, De Camilli P (2002) Dynamin at actin tails. Proc Natl Acad Sci U S A 99:161–166PubMedCrossRefGoogle Scholar
  50. 50.
    Bruzzaniti A, Neff L, Sanjay A, Horne WC, De Camilli P, Baron R (2005) Dynamin forms a Src kinase-sensitive complex with Cbl and regulates podosomes and osteoclast activity. Mol Biol Cell 16:3301–3313PubMedCrossRefGoogle Scholar
  51. 51.
    Tosoni D, Cestra G (2009) CAP (Cbl associated protein) regulates receptor-mediated endocytosis. FEBS Lett 583:293–300PubMedCrossRefGoogle Scholar
  52. 52.
    Sanjay A, Houghton A, Neff L, DiDomenico E, Bardelay C, Antoine E, Levy J, Gailit J, Bowtell D, Horne WC et al (2001) Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v)beta(3) integrin-mediated signaling, cell adhesion, and osteoclast motility. J Cell Biol 152:181–195PubMedCrossRefGoogle Scholar
  53. 53.
    Ribon V, Herrera R, Kay BK, Saltiel AR (1998) A role for CAP, a novel, multifunctional Src homology 3 domain-containing protein in formation of actin stress fibers and focal adhesions. J Biol Chem 273:4073–4080PubMedCrossRefGoogle Scholar
  54. 54.
    Caswell PT, Norman JC (2006) Integrin trafficking and the control of cell migration. Traffic 7:14–21PubMedCrossRefGoogle Scholar
  55. 55.
    Bucci C, Bakke O, Progida C (2012) Charcot–Marie–Tooth disease and intracellular traffic. Prog Neurobiol 99:191–225PubMedCrossRefGoogle Scholar
  56. 56.
    Koutsopoulos OS, Koch C, Tosch V, Bohm J, North KN, Laporte J (2011) Mild functional differences of dynamin 2 mutations associated to centronuclear myopathy and Charcot–Marie–Tooth peripheral neuropathy. PLoS One 6:e27498PubMedCrossRefGoogle Scholar
  57. 57.
    Liu YW, Lukiyanchuk V, Schmid SL (2011) Common membrane trafficking defects of disease-associated dynamin 2 mutations. Traffic 12:1620–1633PubMedCrossRefGoogle Scholar
  58. 58.
    Sidiropoulos PN, Miehe M, Bock T, Tinelli E, Oertli CI, Kuner R, Meijer D, Wollscheid B, Niemann A, Suter U (2012) Dynamin 2 mutations in Charcot–Marie–Tooth neuropathy highlight the importance of clathrin-mediated endocytosis in myelination. Brain 135:1395–1411PubMedCrossRefGoogle Scholar
  59. 59.
    Wu X, Reddy DS (2012) Integrins as receptor targets for neurological disorders. Pharmacol Ther 134:68–81PubMedCrossRefGoogle Scholar
  60. 60.
    Ervasti JM (2003) Costameres: the Achilles’ heel of Herculean muscle. J Biol Chem 278:13591–13594PubMedCrossRefGoogle Scholar
  61. 61.
    Dalkilic I, Kunkel LM (2003) Muscular dystrophies: genes to pathogenesis. Curr Opin Genet Dev 13:231–238PubMedCrossRefGoogle Scholar
  62. 62.
    Perkins AD, Ellis SJ, Asghari P, Shamsian A, Moore ED, Tanentzapf G (2010) Integrin-mediated adhesion maintains sarcomeric integrity. Dev Biol 338:15–27PubMedCrossRefGoogle Scholar
  63. 63.
    Yuan L, Fairchild MJ, Perkins AD, Tanentzapf G (2010) Analysis of integrin turnover in fly myotendinous junctions. J Cell Sci 123:939–946PubMedCrossRefGoogle Scholar
  64. 64.
    Ribeiro I, Yuan L, Tanentzapf G, Dowling JJ, Kiger A (2011) Phosphoinositide regulation of integrin trafficking required for muscle attachment and maintenance. PLoS Genet 7:e1001295PubMedCrossRefGoogle Scholar
  65. 65.
    Laporte J, Hu LJ, Kretz C, Mandel JL, Kioschis P, Coy JF, Klauck SM, Poustka A, Dahl N (1996) A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet 13:175–182PubMedCrossRefGoogle Scholar
  66. 66.
    Bitoun M, Durieux AC, Prudhon B, Bevilacqua JA, Herledan A, Sakanyan V, Urtizberea A, Cartier L, Romero NB, Guicheney P (2009) Dynamin 2 mutations associated with human diseases impair clathrin-mediated receptor endocytosis. Hum Mutat 30:1419–1427PubMedCrossRefGoogle Scholar
  67. 67.
    Cestra G, Toomre D, Chang S, De Camilli P (2005) The Abl/Arg substrate ArgBP2/nArgBP2 coordinates the function of multiple regulatory mechanisms converging on the actin cytoskeleton. Proc Natl Acad Sci U S A 102:1731–1736PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Laura Briñas
    • 1
    • 2
    • 3
    • 4
  • Stéphane Vassilopoulos
    • 1
    • 2
    • 3
    • 4
  • Gisèle Bonne
    • 1
    • 2
    • 3
    • 4
    • 5
  • Pascale Guicheney
    • 6
  • Marc Bitoun
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Université Pierre et Marie Curie-Paris 6, UM76ParisFrance
  2. 2.Inserm, U974ParisFrance
  3. 3.CNRS, UMR 7215ParisFrance
  4. 4.Institut de MyologieParisFrance
  5. 5.Service de Biochimie Métabolique, U.F. Cardiogénétique et Myogénétique, Groupe Hospitalier Pitié-SalpêtrièreAP-HPParisFrance
  6. 6.Inserm, U956ParisFrance

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