Cells contain elaborate and interconnected networks of protein polymers, which make up the cytoskeleton. The cytoskeleton governs the internal positioning and movement of vesicles and organelles and controls dynamic changes in cell polarity, shape, and movement. Many of these processes require tight control of the size and shape of cytoskeletal structures, which is achieved despite rapid turnover of their molecular components. Here we review mechanisms by which cells control the size of filamentous cytoskeletal structures, from the point of view of simple quantitative models that take into account stochastic dynamics of their assembly and disassembly. Significantly, these models make experimentally testable predictions that distinguish different mechanisms of length control. Although the primary focus of this review is on cytoskeletal structures, we believe that the broader principles and mechanisms discussed herein will apply to a range of other subcellular structures whose sizes are tightly controlled and are linked to their functions.


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Literature Cited

  1. Andrianantoandro E, Pollard TD. 1.  2006. Mechanism of actin filament turnover by severing and nucleation at different concentrations of ADF/cofilin. Mol. Cell 24:113–23 [Google Scholar]
  2. Avasthi P, Marshall WF. 2.  2012. Stages of ciliogenesis and regulation of ciliary length. Differ. Res. Biol. Divers. 83:2S30–42 [Google Scholar]
  3. Balcer HI, Goodman AL, Rodal AA, Smith E, Kugler J. 3.  et al. 2003. Coordinated regulation of actin filament turnover by a high-molecular-weight Srv2/CAP complex, cofilin, profilin, and Aip1. Curr. Biol. 13:242159–69 [Google Scholar]
  4. Burke TA, Christensen JR, Barone E, Suarez C, Sirotkin V, Kovar DR. 4.  2014. Homeostatic actin cytoskeleton networks are regulated by assembly factor competition for monomers. Curr. Biol. 24:5579–85 [Google Scholar]
  5. Buttery SM, Yoshida S, Pellman D. 5.  2007. Yeast formins Bni1 and Bnr1 utilize different modes of cortical interaction during the assembly of actin cables. Mol. Biol. Cell 18:51826–38 [Google Scholar]
  6. Chaudhry F, Breitsprecher D, Little K, Sharov G, Sokolova O, Goode BL. 6.  2013. Srv2/cyclase-associated protein forms hexameric shurikens that directly catalyze actin filament severing by cofilin. Mol. Biol. Cell 24:131–41 [Google Scholar]
  7. Chesarone M, Gould CJ, Moseley JB, Goode BL. 7.  2009. Displacement of formins from growing barbed ends by bud14 is critical for actin cable architecture and function. Dev. Cell 16:2292–302 [Google Scholar]
  8. Chesarone-Cataldo M, Guérin C, Yu JH, Wedlich-Soldner R, Blanchoin L, Goode BL. 8.  2011. The myosin passenger protein Smy1 controls actin cable structure and dynamics by acting as a formin damper. Dev. Cell 21:2217–30 [Google Scholar]
  9. Díaz-Valencia JD, Morelli MM, Bailey M, Zhang D, Sharp DJ, Ross JL. 9.  2011. Drosophila katanin-60 depolymerizes and severs at microtubule defects. Biophys. J. 100:102440–49 [Google Scholar]
  10. Dogterom M, Félix MA, Guet CC, Leibler S. 10.  1996. Influence of M-phase chromatin on the anisotropy of microtubule asters. J. Cell Biol. 133:1125–40 [Google Scholar]
  11. Elam WA, Kang H, De la Cruz EM. 11.  2013. Biophysics of actin filament severing by cofilin. FEBS Lett. 587:81215–19 [Google Scholar]
  12. Erlenkämper C, Kruse K. 12.  2009. Uncorrelated changes of subunit stability can generate length-dependent disassembly of treadmilling filaments. Phys. Biol. 6:4046016 [Google Scholar]
  13. Fygenson DK, Braun E, Libchaber A. 13.  1994. Phase diagram of microtubules. Phys. Rev. E 50:21579–88 [Google Scholar]
  14. Gandhi M, Achard V, Blanchoin L, Goode BL. 14.  2009. Coronin switches roles in actin disassembly depending on the nucleotide state of actin. Mol. Cell 34:3364–74 [Google Scholar]
  15. Gardner MK, Zanic M, Howard J. 15.  2013. Microtubule catastrophe and rescue. Curr. Opin. Cell Biol. 25:114–22 [Google Scholar]
  16. Ghaemmaghami S, Huh W-K, Bower K, Howson RW, Belle A. 16.  et al. 2003. Global analysis of protein expression in yeast. Nature 425:6959737–41 [Google Scholar]
  17. Goehring NW, Hyman AA. 17.  2012. Organelle growth control through limiting pools of cytoplasmic components. Curr. Biol. 22:9R330–39 [Google Scholar]
  18. Goshima G, Wollman R, Stuurman N, Scholey JM, Vale RD. 18.  2005. Length control of the metaphase spindle. Curr. Biol. 15:221979–88 [Google Scholar]
  19. Gould CJ, Chesarone-Cataldo M, Alioto SL, Salin B, Sagot I, Goode BL. 19.  2014. Saccharomyces cerevisiae Kelch proteins and Bud14 protein form a stable 520-kDa formin regulatory complex that controls actin cable assembly and cell morphogenesis. J. Biol. Chem. 289:2618290–301 [Google Scholar]
  20. Graziano BR, Yu H-YE, Alioto SL, Eskin JA, Ydenberg CA. 20.  et al. 2014. The F-BAR protein Hof1 tunes formin activity to sculpt actin cables during polarized growth. Mol. Biol. Cell 25:111730–43 [Google Scholar]
  21. Greenan G, Brangwynne CP, Jaensch S, Gharakhani J, Jülicher F, Hyman AA. 21.  2010. Centrosome size sets mitotic spindle length in Caenorhabditis elegans embryos. Curr. Biol. 20:4353–58 [Google Scholar]
  22. Gurdon JB.22.  1976. Injected nuclei in frog oocytes: fate, enlargement, and chromatin dispersal. J. Embryol. Exp. Morphol. 36:3523–40 [Google Scholar]
  23. Henty-Ridilla JL, Goode BL. 23.  2015. Global resource distribution: allocation of actin building blocks by profilin. Dev. Cell 32:15–6 [Google Scholar]
  24. Ishikawa H, Marshall WF. 24.  2011. Ciliogenesis: building the cell's antenna. Nat. Rev. Mol. Cell Biol. 12:4222–34 [Google Scholar]
  25. Jansen S, Collins A, Chin SM, Ydenberg CA, Gelles J, Goode BL. 25.  2015. Single-molecule imaging of a three-component ordered actin disassembly mechanism. Nat. Commun. 6:7202 [Google Scholar]
  26. Johann D, Erlenkämper C, Kruse K. 26.  2012. Length regulation of active biopolymers by molecular motors. Phys. Rev. Lett. 108:25258103 [Google Scholar]
  27. Johnston AB, Collins A, Goode BL. 27.  2015. High speed depolymerization at actin filament ends jointly catalysed by Twinfilin and Srv2/CAP. Nat. Cell Biol. 17:1504–11 [Google Scholar]
  28. Kirkham M, Müller-Reichert T, Oegema K, Grill S, Hyman AA. 28.  2003. SAS-4 is a C. elegans centriolar protein that controls centrosome size. Cell 112:4575–87 [Google Scholar]
  29. Kovar DR, Pollard TD. 29.  2004. Insertional assembly of actin filament barbed ends in association with formins produces piconewton forces. PNAS 101:4114725–30 [Google Scholar]
  30. Kuan H-S, Betterton MD. 30.  2013. Biophysics of filament length regulation by molecular motors. Phys. Biol. 10:3036004 [Google Scholar]
  31. Kueh HY, Charras GT, Mitchison TJ, Brieher WM. 31.  2008. Actin disassembly by cofilin, coronin, and Aip1 occurs in bursts and is inhibited by barbed-end cappers. J. Cell Biol. 182:2341–53 [Google Scholar]
  32. Kuhn TB, Bamburg JR. 32.  2008. Tropomyosin and ADF/cofilin as collaborators and competitors. Adv. Exp. Med. Biol. 644:232–49 [Google Scholar]
  33. Lin HW, Schneider ME, Kachar B. 33.  2005. When size matters: the dynamic regulation of stereocilia lengths. Curr. Opin. Cell Biol. 17:155–61 [Google Scholar]
  34. Manor U, Kachar B. 34.  2008. Dynamic length regulation of sensory stereocilia. Semin. Cell Dev. Biol. 19:6502–10 [Google Scholar]
  35. Marshall WF, Qin H, Rodrigo Brenni M, Rosenbaum JL. 35.  2005. Flagellar length control system: testing a simple model based on intraflagellar transport and turnover. Mol. Biol. Cell 16:1270–78 [Google Scholar]
  36. Marshall WF, Rosenbaum JL. 36.  2001. Intraflagellar transport balances continuous turnover of outer doublet microtubules: implications for flagellar length control. J. Cell Biol. 155:3405–14 [Google Scholar]
  37. Melbinger A, Reese L, Frey E. 37.  2012. Microtubule length regulation by molecular motors. Phys. Rev. Lett. 108:25258104 [Google Scholar]
  38. Mitchell DR.38.  2004. Speculations on the evolution of 9+2 organelles and the role of central pair microtubules. Biol. Cell 96:9691–96 [Google Scholar]
  39. Mitchell DR.39.  2007. The evolution of eukaryotic cilia and flagella as motile and sensory organelles. Adv. Exp. Med. Biol. 607:130–40 [Google Scholar]
  40. Mohapatra L, Goode BL, Kondev J. 40.  2015. Antenna mechanism of length control of actin cables. PLOS Comput. Biol. 11:6e1004160 [Google Scholar]
  41. Niwa S, Nakajima K, Miki H, Minato Y, Wang D, Hirokawa N. 41.  2012. KIF19A is a microtubule-depolymerizing kinesin for ciliary length control. Dev. Cell 23:61167–75 [Google Scholar]
  42. Pavlov D, Muhlrad A, Cooper J, Wear M, Reisler E. 42.  2007. Actin filament severing by cofilin. J. Mol. Biol. 365:51350–58 [Google Scholar]
  43. Phillips R, Kondev J, Theriot J, Garcia H. 43.  2012. Physical Biology of the Cell London/New York: Garland Science, 2nd. [Google Scholar]
  44. Pollard TD.44.  1986. Rate constants for the reactions of ATP- and ADP-actin with the ends of actin filaments. J. Cell Biol. 103:6, Pt. 22747–54 [Google Scholar]
  45. Rafelski SM, Viana MP, Zhang Y, Chan Y-HM, Thorn KS. 45.  et al. 2012. Mitochondrial network size scaling in budding yeast. Science 338:6108822–24 [Google Scholar]
  46. Reese L, Melbinger A, Frey E. 46.  2014. Molecular mechanisms for microtubule length regulation by kinesin-8 and XMAP215 proteins. Interface Focus 4:620140031 [Google Scholar]
  47. Roland J, Berro J, Michelot A, Blanchoin L, Martiel J-L. 47.  2008. Stochastic severing of actin filaments by actin depolymerizing factor/cofilin controls the emergence of a steady dynamical regime. Biophys. J. 94:62082–94 [Google Scholar]
  48. Rotty JD, Wu C, Haynes EM, Suarez C, Winkelman JD. 48.  et al. 2015. Profilin-1 serves as a gatekeeper for actin assembly by Arp2/3-dependent and -independent pathways. Dev. Cell 32:154–67 [Google Scholar]
  49. Skau CT, Kovar DR. 49.  2010. Fimbrin and tropomyosin competition regulates endocytosis and cytokinesis kinetics in fission yeast. Curr. Biol. 20:161415–22 [Google Scholar]
  50. Suarez C, Carroll RT, Burke TA, Christensen JR, Bestul AJ. 50.  et al. 2015. Profilin regulates F-actin network homeostasis by favoring formin over Arp2/3 complex. Dev. Cell 32:143–53 [Google Scholar]
  51. Varga V, Helenius J, Tanaka K, Hyman AA, Tanaka TU, Howard J. 51.  2006. Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner. Nat. Cell Biol. 8:9957–62 [Google Scholar]
  52. Varga V, Leduc C, Bormuth V, Diez S, Howard J. 52.  2009. Kinesin-8 motors act cooperatively to mediate length-dependent microtubule depolymerization. Cell 138:61174–83 [Google Scholar]
  53. Weber SC, Brangwynne CP. 53.  2015. Inverse size scaling of the nucleolus by a concentration-dependent phase transition. Curr. Biol. 25:5641–46 [Google Scholar]
  54. Yu JH, Crevenna AH, Bettenbühl M, Freisinger T, Wedlich-Söldner R. 54.  2011. Cortical actin dynamics driven by formins and myosin V. J. Cell Sci. 124:91533–41 [Google Scholar]

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