Abstract
In this review we consider the multiple functions of developmentally regulated brain protein (drebrin), an actin-binding protein, in the formation of cellular polarity in different cell types. Drebrin has a well-established role in the morphogenesis, patterning and maintenance of dendritic spines in neurons. We have recently shown that drebrin also stabilizes Connexin-43 containing gap junctions at the plasma membrane. The latest literature and our own data suggest that drebrin may be broadly involved in shaping cell processes and in the formation of stabilized plasma membrane domains, an effect that is likely to be of crucial significance for formation of cell polarity in both neuronal and non-neuronal types.
Similar content being viewed by others
References
Bass PW, Black MM, Banker GA (1989) Changes in microtubule plarity orientation during the development of hippocampal neurons in culture. J Cell Biol 109:3085–3094
Bradke F, Dotti CG (2000) Establishment of neuronal polarity: lessons from cultured hippocampal neurons. Curr Opin Neurobiol 10:574–581
Buccione R, Orth JD, McNiven MA (2004) Foot and mouth: podosomes, invadopodia and circular dorsal ruffles. Nat Rev Mol Cell Biol 5:647–657
Bukauskas FF, Jordan K, Bukauskiene A, Bennett MV, Lampe PD, Laird DW, Verselis VK (2000) Clustering of connexin 43-enhanced green fluorescent protein gap junction channels and functional coupling in living cells. Proc Natl Acad Sci USA 97:2556–2561
Butkevich E, Hulsmann S, Wenzel D, Shirao T, Duden R, Majoul I (2004) Drebrin stabilizes connexin-43 and links gap junctions to the sub-membrane cytoskeleton. Curr Biol 14:650–658
Craig AM, Banker G (1994) Neuronal polarity. Annu Rev Neurosci 17:267–310
Dotti CG, Banker G (1987). Experimentally induced alteration in the polarity of developing neurons. Nature 330:254–256
Dotti CG, Sullivan CA, Banker GA (1988) The establishment of polarity by hippocampal neurons in culture. J Neurosci 8:1454–1468
Goldberg GS, Lampe PD, Nicholson BJ (1999) Selective transfer of endogenous metabolites through gap junctions composed of different connexins. Nat Cell Biol 1:457–459
Goslin K, Banker G (1989) Experimental observations on the development of polarity by hippocampal neurons in culture. J Cell Biol 108:1507–1516
Harigaya Y, Shoji M, Shirao T, Hirai S (1996) Disappearance of actin-binding protein, drebrin, from hippocampal synapses in Alzheimer’s disease. J Neurosci Res 43:87–92
Hatanpaa K, Isaacs KR, Shirao T, Brady DR, Rapoport SI (1999) Loss of proteins regulating synaptic plasticity in normal aging of the human brain and in Alzheimer disease. J Neuropathol Exp Neurol 58:637–643
Hayashi K, Shirao T (1999) Change in the shape of dendritic spines caused by overexpression of drebrin in cultured cortical neurons. J Neurosci 19:3918–3925
Hayashi K, Ishikawa R, Ye LH, Takata K, Kohama K, Shirao T (1996) Modulatory role of drebrin in the cytoskeleton within dendritic spines in the rat cerebral cortex. J Neurosci 16:7161–7170
Hayashi K, Ishikawa R, Kawai-Hirai R, Takagi T, Taketomi A, Shirao T (1999) Domain analysis of the actin-binding and actin-remodeling activities of drebrin. Exp Cell Res 253:673–680
Huang Z, Zang K, Reichardt LF (2005) The origin recognition core complex regulates dendrite and spine development in postmitotic neurons. J Cell Biol 170:527–535
Inoue HK, Shirao T (1997) Neurite formation induced in neuroblastoma cells and genetically altered non-neuronal cells. J Electron Microsc (Tokyo) 46:497–502
Ishikawa R, Hayashi K, Shirao T, Xue Y, Takagi T, Sasaki Y, Kohama K (1994) Drebrin, a development-associated brain protein from rat embryo, causes the dissociation of tropomyosin from actin filaments. J Biol Chem 269:29928–29933
Jamora C, Fuchs E (2002) Intercellular adhesion, signalling and the cytoskeleton. Nat Cell Biol 4:E101–E108
Jin M, Tanaka S, Sekino Y, Ren Y, Yamazaki H, Kawai-Hirai R, Kojima N, Shirao T (2002) A novel, brain-specific mouse drebrin: cDNA cloning, chromosomal mapping, genomic structure, expression, and functional characterization. Genomics 79:686–692
Keller A (2002) Use-dependent inhibition of dendritic spines. Trends Neurosci 25:541–544
Keon BH, Jedrzejewski PT, Paul DL, Goodenough DA (2000) Isoform specific expression of the neuronal F-actin binding protein, drebrin, in specialized cells of stomach and kidney epithelia. J Cell Sci 113:325–336
Kobayashi RY Sekino, Shirao T, Tanaka S, Ogura T, Inada K, Saji M (2004) Antisense knockdown of drebrin A, a dendritic spine protein, causes stronger preference, impaired pre-pulse inhibition, and an increased sensitivity to psychostimulant. Neurosci Res 49:205–217
Kumar NM, Gilula NB (1996) The gap junction communication channel. Cell 84:381–388
Lappalainen P, Kessels MM, Cope MJ, Drubin DG (1998) The ADF homology (ADF-H) domain: a highly exploited actin-binding module. Mol Biol Cell 9:1951–1959
Linder S., Aepfelbacher M (2003) Podosomes: adhesion hot-spots of invasive cells. Trends Cell Biol 13:376–385
Macara IG (2004) Par proteins: partners in polarization. Curr Biol 14:R160–R162
Marrs GS, Green SH, Dailey ME (2001) Rapid formation and remodeling of postsynaptic dendrites in developing dendrites. Nat Neurosci 4:1006–1013
Mizui T, Takahashi H, Sekino Y, Shirao T (2005) Overexpression of drebrin A in immature neurons induces the accumulation of F-actin and PSD-95 into dendritic filopodia, and the formation of large abnormal protrusions. Mol Cell Neurosci 30:149–157
Nishimura T, Kato K, Yamaguchi T, Fukata Y, Ohno S, Kaibuchi K (2004) Role of the PAR-3–KIF3 complex in the establishment of neuronal polarity. Nat Cell Biol 6:328–334
Okabe S, Miwa A, Okado H (2001) Spine formation and correlated assembly of presynaptic and postsynaptic molecules. J Neurosci 21:6105–6114
Peitsch WK, Grund C, Kuhn C, Schnolzer M, Spring H, Schmelz M, Franke WW (1999) Drebrin is a widespread actin-associating protein enriched at junctional plaques, defining a specific microfilament anchorage system in polar epithelial cells. Eur J Cell Biol 78:767–778
Peitsch WK, Hofmann I, Pratzel S, Grund C, Kuhn C, Moll I, Langbein L, Franke WW (2001) Drebrin particles: components in the ensemble of proteins regulating actin dynamics of lamellipodia and filopodia. Eur J Cell Biol 80:567–579
Peitsch WK, Hofmann I, Bulkescher J, Hergt M, Spring H, Bleyl U, Goerdt S, Franke WW (2005) Drebrin, an actin-binding, cell-type characteristic protein: induction and localization in epithelial skin tumors and cultured keratinocytes. J Invest Dermatol 125:761–774
Peitsch WK, Bulkescher J, Spring H, Hofmann I, Goerdt S, Franke WW (2006) Dynamics of the actin-binding protein drebrin in motile cells and definition of a juxtanuclear drebrin-enriched zone. Exp Cell Res 312:2605–2618
Schwamborn JC, Puschel AW (2004) The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity. Nat Neurosci 7:923–929
Shi SH, Jan LY, Jan YN (2003) Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity. Cell 112:63–75
Shim KS, Lubec G (2002) Drebrin, a dendritic spine protein, is manifold decreased in brains of patients with Alzheimer’s disease and Down syndrome. Neurosci Lett 324:209–212
Shirao T (1995) The roles of microfilament-associated proteins, drebrins, in brain morphogenesis: a review. J Biochem (Tokyo) 117:231–236
Shirao T, Obata K (1986) Immunochemical homology of 3 developmentally regulated brain proteins and their developmental change in neuronal distribution. Brain Res 394:233–244
Shirao T, Sekino Y (2001) Clustering and anchoring mechanisms of molecular constituents of postsynaptic scaffolds in dendritic spines. Neurosci Res 40:1–7
Shirao T, Kojima N, Kato Y, Obata K (1988) Molecular cloning of a cDNA for the developmentally regulated brain protein, drebrin. Brain Res 464:71–74
Shirao T, Hayashi K, Ishikawa R, Isa K, Asada H, Ikeda K, Uyemura K (1994) Formation of thick curving bundles of actin by drebrin A expressed in fibroblasts. Exp Cell Res 215:145–153
Spinardi L, Rietdorf J, Nitsch L, Bono M, Tacchetti C, Way M, Marchisio PC (2004) A dynamic podosome-like structure of epithelial cells. Exp Cell Res 295:360–374
Stout C, Goodenough DA, Paul DL (2004) Connexins: functions without junctions. Curr Opin Cell Biol 16:507–512
Takahashi H, Mizui T, Shirao T (2006) Down-regulation of drebrin A expression suppresses synaptic targeting of NMDA receptors in developing hippocampal neurons. J Neurochem 97(Suppl 1):110–115
Takeda S, Yamazaki H, Seog DH, Kanai Y, Terada S, Hirokawa N (2000) Kinesin superfamily protein 3 (KIF3) motor transports fodrin-associating vesicles important for neurite building. J Cell Biol 148:1255–1265
Wiggin GR, Fawcett JP, Pawson T (2005) Polarity proteins in axon specification and synaptogenesis. Dev Cell 8:803–816
Acknowledgments
The authors are grateful to Drs. Eugenia Butkevich and Piotr Bregestovski for critical reading of early versions of this manuscript. We thank Dr. Robin Battye (Quorum Technologies; http://www.quorumtechnologies.com/) for his invaluable help with long-time imaging of cells expressing drebrin, at the “3D Microscopy of Living Cells” course held in 2006 at the University of British Columbia, Vancouver, Canada (http://www.3dcourse.ubc.ca/index.htm). This work was supported by the Wellcome Trust (Senior Fellowship to R.D.; grant number 047578).
Author information
Authors and Affiliations
Corresponding authors
Electronic supplementary material
Below is the link to the electronic supplementary material.
Movie 1 (AVI 8.9 mb)
Rights and permissions
About this article
Cite this article
Majoul, I., Shirao, T., Sekino, Y. et al. Many faces of drebrin: from building dendritic spines and stabilizing gap junctions to shaping neurite-like cell processes . Histochem Cell Biol 127, 355–361 (2007). https://doi.org/10.1007/s00418-007-0273-y
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-007-0273-y