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Colocalization of BCR protein with clathrin, actin, and cortactin suggests its possible role in the regulation of actin branching and clathrin-mediated endocytosis

Gurianov D.S., Antonenko S.V., Telegeev G.D.


SUMMARY. Philadelphia chromosome is a result of reciprocal translocation between chromosomes 9 and 22 and serves as a distinct marker of several types of myeloproliferative disorders. Such translocation generates different types of fusions of bcr and abl genes. These fusions differ in presence or absence of certain types of BCR domains and in molecular weight of corresponding chimeric proteins. BCR-ABLp230 is associated with chronic neutrophilic leukemia, BCR-ABLp210 with chronic myelogenous leukemia, BCR-ABLp190 with acute lymphoblastic leukemia. Pleckstrin homology domain of BCR is present in p210 and absent in p190 type of fusion protein. Mass-spectromic analysis previously identified 23 potential candidates for interaction with PH domain, including cortactin that is responsible for actin branching. In present work we show that BCR protein colocalized with actin and cortactin at K562 cells periphery. It also formed clusters of colocalization with clathrin and cortactin and was located at points of actin branching, which was shown by STED super-resolution microscopy and regular confocal microscopy of live HEK 293T cells. Live confocal microscopy also identified a relatively large structure in cytoplasm where dynamic comovement of BCR, clathrin and actin occurred. This strongly resembles Golgi complex, as trans-Golgi network is a typical location of clathrin-coated vesicle sorting and assembly. Our findings indicate that BCR in tandem with cortactin may have an important role in dynamic actin-membrane rearrangements that affect clathrin-mediated endocytosis and Golgi vesicular transport. The disruption of its function by abnormal tyrosine kinase activity of ABL may promote cancer phenotype.

Key words: Bacillus subtilis, riboflavin, mutagenesis, phylogeny, UV radiation, producer strain

Tsitologiya i Genetika 2021, vol. 55, no. 2, pp. 56-67

  • Institute of Molecular Biology and Genetics of NASU

E-mail: dmitriy.gurianov

Gurianov D.S., Antonenko S.V., Telegeev G.D. Colocalization of BCR protein with clathrin, actin, and cortactin suggests its possible role in the regulation of actin branching and clathrin-mediated endocytosis, Tsitol Genet., 2021, vol. 55, no. 2, pp. 56-67.

In "Cytology and Genetics":
D. S. Gurianov, S. V. Antonenko & G. D. Telegeev Colocalization of BCR Protein with Clathrin, Actin, and Cortactin Suggests Its Possible Role in the Regulation of Actin Branching and Clathrin-Mediated Endocytosis, Cytol Genet., 2021, vol. 55, no. 2, pp. 152161
DOI: 10.3103/S0095452721020055


1. Aigouy, B. and Mirouse, V., ScientiFig: a tool to build publication-ready scientific figures, Nat. Methods, 2013, vol. 10, p. 1048.

2. Antonenko, S.V., Kravchuk, I.V., and Telegeev, G.D., Interaction of Bcl-Abl oncoprotein with the Glg1 protein in K562 cells: its role in the pathogenesis of chronic myeloid leukemia, Cytol. Genet., 2020.

3. Bard, F. and Malhotra, V., The formation of TGN-to-plasma-membrane transport carriers, Annu. Rev. Cell Dev. Biol., 2006, vol. 22, pp. 439455.

4. Birnboim, H.C. and Doly, J., A rapid alkaline extraction procedure for screening recombinant plasmid DNA, Nucleic Acids Res., 1979, vol. 7, pp. 15131523.

5. Bolte, S. and Cordelieres, F.P., A guided tour into subcellular colocalization analysis in light microscopy, J. Microsc., 2006, vol. 224, pp. 213232.

6. Cao, H., Orth, J.D., Chen, J., et al., Cortactin is a component of clathrin-coated pits and participates in receptor-mediated endocytosis, Mol. Cell Biol., 2003, vol. 23, pp. 21622170.

7. Cao, H., Weller, S., Orth, J.D., et al., Actin and Arf1-dependent recruitment of a cortactindynamin complex to the Golgi regulates post-Golgi transport, Nat. Cell Biol., 2005, vol. 7, pp. 483492.

8. Chen, J.L., Lacomis, L., Erdjument-Bromage, H., et al., Cytosol-derived proteins are sufficient for Arp2/3 recruitment and ARF/coatomer-dependent actin polymerization on Golgi membranes, FEBS Lett., 2004, vol. 566, pp. 281286. 2004.04.061

9. Chen, L., Wang, Z.-W., Zhu, J., and Zhan, X., Roles of cortactin, an actin polymerization mediator, in cell endocytosis, Acta Biochim. Biophys. Sin. (Shanghai), 2006, vol. 38, pp. 95103.

10. Chen, P.H., Yao, H., and Huang, L.J.S., Cytokine receptor endocytosis: new kinase activity-dependent and -independent roles of PI3K, Front. Endocrinol. (Lausanne), 2017, vol. 8.

11. Cho, Y.J., Cunnick, J.M., Yi, S.-.J., et al., Abr and Bcr, two homologous Rac GTPase-activating proteins, control multiple cellular functions of murine macrophages, Mol. Cell Biol., 2007, vol. 27, pp. 899911.

12. Daboussi, L., Costaguta, G., and Payne, G.S., Phosphoinositide-mediated clathrin adaptor progression at the trans-Golgi network, Nat. Cell Biol., 2012, vol. 14, pp. 239248.

13. Dey, N., Blanc-Feraud, L., Zimmer, C., et al., RichardsonLucy algorithm with total variation regularization for 3D confocal microscope deconvolution, Microsc. Res. Tech., 2006, vol. 69, pp. 260266.

14. Emilia, G., Luppi, M., Marasca, R., and Torelli, G., Relationship between BCR/ABL fusion proteins and leukemia phenotype, Blood, 1997, vol. 89, pp. 38893889.

15. Gordon, M.Y., Dowding, C.R., Riley, G.P., et al., Altered adhesive interactions with marrow stroma of haematopoietic progenitor cells in chronic myeloid leukaemia, Nature, 1988, vol. 328, pp. 342344.

16. Groffen, J., Stephenson, J.R., Heisterkamp, N., et al., Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22, Cell, 1984, vol. 36, pp. 9399. (84)90077-1

17. Gu, C., Yaddanapudi, S., Weins, A., et al., Direct dynaminactin interactions regulate the actin cytoskeleton, EMBO J., 2010, vol. 29, pp. 359335606.

18. Holst, M.R., Vidal-Quadras, M., Larsson, E., et al., Clathrin-independent endocytosis suppresses cancer cell blebbing and invasion, Cell Rep., 2017, vol. 20, pp. 18931905.

19. Huang, S. and Wang, Y., Golgi structure formation, function, and post-translational modifications in mammalian cells, F1000Research, 2017, vol. 6, p. 2050.

20. Kirkbride, K.C., Hong, N.H., French, C.L., et al., Regulation of late endosomal/lysosomal maturation and trafficking by cortactin affects Golgi morphology, Cytoskeleton, 2012, vol. 69, pp. 625643.

21. Kirshner, H., Aguet, F., Sage, D., and Unser, M., 3-D PSF fitting for fluorescence microscopy: implementation and localization application, J. Microsc., 2013, vol. 249, pp. 1325.

22. Lemmon, M.A., Pleckstrin homology domains: not just for phosphoinositides, Biochem. Soc. Trans., 2004, vol. 32, pp. 707711.

23. Lemmon, M.A. and Ferguson, K.M., Signal-dependent membrane targeting by pleckstrin homology (PH) domains, Biochem. J., 2000, vol. 350, p. 1.

24. Lemmon, M.A., Ferguson, K.M., and Abrams, C.S., Pleckstrin homology domains and the cytoskeleton, FEBS Lett., 2002, vol. 513, pp. 7176.

25. Manders, E.M.M., Verbeek, F.J., and Aten, J.A., Measurement of co-localization of objects in dual-colour confocal images, J. Microsc., 1993, vol. 169, pp. 375382.

26. Mayinger, P., Regulation of Golgi function via phosphoinositide lipids, Semin. Cell Dev. Biol., 2009, vol., 20, pp. 793 800.

27. Miroshnychenko, D., Dubrovska, A., Maliuta, S., et al., Novel role of pleckstrin homology domain of the Bcr-Abl protein: analysis of protein-protein and protein-lipid interactions, Exp. Cell Res., 2010, vol. 316, pp. 530542.

28. Narayanan, A.S., Reyes, S.B., Um, K., et al., The Rac-GAP Bcr is a novel regulator of the Par complex that controls cell polarity, Mol. Biol. Cell, 2013, vol. 24, pp. 38573868.

29. Sage, D., Donati, L., Soulez, F., et al., DeconvolutionLab2: an open-source software for deconvolution microscopy, Methods, 2017, vol. 115, pp. 2841.

30. Sauer, M.-L., Kollars, B., Geraets, R., and Sutton, F., Sequential CaCl2, polyethylene glycol precipitation for RNase-free plasmid DNA isolation, Anal. Biochem., 2008, vol. 380, pp. 310314.

31. Schindelin, J., Arganda-Carreras, I., Frise, E., et al., Fiji: an open source platform for biological image analysis, Nat. Methods, 2012, vol. 9, pp. 676682.

32. Shannon, C.E., Communication in the presence of noise, Proc. IEEE, 1998, vol. 86, pp. 447457.

33. Steen, W., Principles of Optics, Born, M. and Wolf, E., Eds., 7th ed. (expanded), Cambridge: Cambridge University Press, 1999, ISBN 0-521-64222-1. Opt Laser Technol 32:385.

34. Underhill-Day, N., Pierce, A, Thompson, S.E., et al., Role of the C-terminal actin binding domain in BCR/ABL-mediated survival and drug resistance, Br. J. Haematol., 2006, vol. 132, pp. 774783.

35. Van Etten, R.A., The molecular pathogenesis of the Philadelphia-positive leukemias: implications for diagnosis and therapy, Cancer Treat. Res., 1993, pp. 295325.

36. Van Etten, R.A., Aberrant cytokine signaling in leukemia, Oncogene, 2007, vol. 26, pp. 67386749.

37. Waugh, M.G., The Great Escape: how phosphatidylinositol 4-kinases and PI4P promote vesicle exit from the Golgi (and drive cancer), Biochem. J., 2019, vol. 476, pp. 23212346.

38. Weaver, A.M., Cortactin in tumor invasiveness, Cancer Lett., 2008, vol. 265, pp. 157166.

39. Whittaker, E.T., XVIII. On the functions which are represented by the expansions of the interpolationtheory, Proc. R. Soc. Edinburgh, 1915, vol. 35, pp. 181194.

40. Yan, J., Wen, W., Xu, W., et al.,) Structure of the split PH domain and distinct lipid-binding properties of the PH-PDZ supramodule of alpha-syntrophin, EMBO J., 2005, vol. 24, pp. 39853995.

41. Yarar, D., Waterman-Storer, C.M., and Schmid, S.L., A dynamic actin cytoskeleton functions at multiple stages of clathrin-mediated endocytosis, Mol. Biol. Cell, 2005, vol. 16, pp. 964975.

42. Zhu, J., Zhou, K., Hao, J.-J., et al., Regulation of cortactin/dynamin interaction by actin polymerization during the fission of clathrin-coated pits, J. Cell Sci., 2005, vol. 118, pp. 807817.

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