Bleb Retraction2018-02-06T11:12:07+00:00

Bleb Retraction

Retraction generally lasts between 60 to 120 seconds [1]. When the cells membrane lacks the stability afforded, for example, by cell-substrate contacts, the primary cascade involved in retraction is that of mysoin-RhoA-ROCK [2]. In this cascade, myosin is recruited to the bleb lumen, GTP-loaded Rho activates ROCK, which directly phosphorylates myosin light chain and so generates actomyosin contraction [3][4][5][6][7].

This process can be regulated at multiple levels, both extracellularly and intracellularly, such as in the case of RhoA, its activity can be regulated by both extracellular signals and intracellular cascades [5].

Indirect regulation of this cascade may also occur via members of the Rac subfamily of Rho GTPases, such as Rac1 [8][9] or Dictyostelium discoideum RacB [10]. The cascade can also be regulated through inhibition of its effector ROCK [6]. In addition, the formins, Dia1 and mDia2 have been shown to be crucial in regulating retraction [11][12].

View All

Latest Findings

Protein Info

References

  1. Charras G, and Paluch E. Blebs lead the way: how to migrate without lamellipodia. Nat. Rev. Mol. Cell Biol. 2008; 9(9):730-6. [PMID: 18628785]
  2. Fackler OT, and Grosse R. Cell motility through plasma membrane blebbing. J. Cell Biol. 2008; 181(6):879-84. [PMID: 18541702]
  3. Paluch E, Piel M, Prost J, Bornens M, and Sykes C. Cortical actomyosin breakage triggers shape oscillations in cells and cell fragments. Biophys. J. 2005; 89(1):724-33. [PMID: 15879479]
  4. Charras GT, Yarrow JC, Horton MA, Mahadevan L, and Mitchison TJ. Non-equilibration of hydrostatic pressure in blebbing cells. Nature 2005; 435(7040):365-9. [PMID: 15902261]
  5. Gadea G, de Toledo M, Anguille C, and Roux P. Loss of p53 promotes RhoA-ROCK-dependent cell migration and invasion in 3D matrices. J. Cell Biol. 2007; 178(1):23-30. [PMID: 17606864]
  6. Kitzing TM, Sahadevan AS, Brandt DT, Knieling H, Hannemann S, Fackler OT, Grosshans J, and Grosse R. Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion. Genes Dev. 2007; 21(12):1478-83. [PMID: 17575049]
  7. Tournaviti S, Hannemann S, Terjung S, Kitzing TM, Stegmayer C, Ritzerfeld J, Walther P, Grosse R, Nickel W, and Fackler OT. SH4-domain-induced plasma membrane dynamization promotes bleb-associated cell motility. J. Cell. Sci. 2007; 120(Pt 21):3820-9. [PMID: 17959630]
  8. Schwartz MA, Meredith JE, and Kiosses WB. An activated Rac mutant functions as a dominant negative for membrane ruffling. Oncogene 1998; 17(5):625-9. [PMID: 9704928]
  9. Vidali L, Chen F, Cicchetti G, Ohta Y, and Kwiatkowski DJ. Rac1-null mouse embryonic fibroblasts are motile and respond to platelet-derived growth factor. Mol. Biol. Cell 2006; 17(5):2377-90. [PMID: 16525021]
  10. Lee E, Seastone DJ, Harris E, Cardelli JA, and Knecht DA. RacB regulates cytoskeletal function in Dictyostelium spp. Eukaryotic Cell 2003; 2(3):474-85. [PMID: 12796292]
  11. Keller H, and Eggli P. Protrusive activity, cytoplasmic compartmentalization, and restriction rings in locomoting blebbing Walker carcinosarcoma cells are related to detachment of cortical actin from the plasma membrane. Cell Motil. Cytoskeleton 1998; 41(2):181-93. [PMID: 9786092]
  12. Eisenmann KM, Harris ES, Kitchen SM, Holman HA, Higgs HN, and Alberts AS. Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex. Curr. Biol. 2007; 17(7):579-91. [PMID: 17398099]