MorphologyMorphologyМорфология1026-35432949-2556Eco-Vector39939110.17816/morph.399391ArticlesСтатьиMICROTUBULE-ASSOCIATED PROTEINS AS MARKERS OF NERVE CELL DIFFERENTIATION AND FUNCTIONAL STATUSБЕЛКИ, АССОЦИИРОВАННЫЕ С МИКРОТРУБОЧКАМИ, КАК ПОКАЗАТЕЛИ ДИФФЕРЕНЦИРОВКИ И ФУНКЦИОНАЛЬНОГО СОСТОЯНИЯ НЕРВНЫХ КЛЕТОКKorzhevskiyD EКоржевскийД Э

Лаборатория функциональной морфологии центральной и периферической нервной системы (руков. - д-р мед. наук Д.Э. Коржевский), отдел общей и частной морфологии; Научно-исследовательский институт экспериментальной медицины СЗО РАМН, Санкт-Петербург

KarpenkoM NКарпенкоМ Н

Лаборатория функциональной морфологии центральной и периферической нервной системы (руков. - д-р мед. наук Д.Э. Коржевский), отдел общей и частной морфологии; Научно-исследовательский институт экспериментальной медицины СЗО РАМН, Санкт-Петербург

KirikO VКирикО В

Лаборатория функциональной морфологии центральной и периферической нервной системы (руков. - д-р мед. наук Д.Э. Коржевский), отдел общей и частной морфологии; Научно-исследовательский институт экспериментальной медицины СЗО РАМН, Санкт-Петербург

KorzhevskiyD EKarpenkoM NKirikO VНаучно-исследовательский институт экспериментальной медицины СЗО РАМН, Санкт-Петербург150320111391NO1 (2011)№1 (2011)132109052023Copyright ©; 2011, Eco-VectorCopyright ©; 2011, Эко-Вектор2011Eco-VectorЭко-Векторhttps://j-morphology.com/1026-3543/article/view/399391

This paper is aimed at the characterization of beta-III-tubulin, MAP2 and doublecortin, the proteins which participate in the organization, stabilization and function of the microtubules of nerve cell cytoskeleton. Due to the structural and functional features, these proteins may be regarded as differentiation markers, associated with neurogenesis and as the indicators of nerve cell functional status under normal and pathological conditions. The data presented show that these proteins perform important structural and transport functions in nerve cells and are essential for some neurospecific intracellular processes. However, current knowledge of the functional role of these proteins in nerve cells is insufficient and requires significant supplementation indispensable for unequivocal interpretation of the studies results.

Настоящая работа посвящена характеристике белков бета-тубулина III, МАР2 и даблкортина, которые участвуют в организации, стабилизации и функционировании микротрубочек цитоскелета нервной клетки. Благодаря своим структурнофункциональным особенностям эти клетки могут рассматриваться в качестве дифференцировочных маркеров, ассоциированных с нейрогенезом, а также показателей функционального состояния нервной клетки в норме и при патологии. Приведенные сведения показывают, что указанные белки выполняют важные структурные и транспортные функции в нервной клетке и необходимы для осуществления нейроспецифических внутриклеточных процессов. Однако имеющиеся знания о функциональной роли этих белков в нервных клетках недостаточны и нуждаются в существенных дополнениях, без которых невозможно однозначно трактовать результаты исследований.

microtubulesneural cellsdoubelcortintubulinнервные клеткимикротрубочкидаблкортинтубулинАлексеева О.С., Коржевский Д.Э., Григорьев И.П. и др. Преадаптация к азотному наркозу и нарушения структуры коры головного мозга крыс при гипоксии. Журн. эволюц. биохим., 2010, т. 46, № 4, с. 311-315.Вердиев Б.И., Полтавцева Р.А., Подгорный О.В. и др. Молекулярно-генетический и иммунотипический анализ транскрипционного фактора Pax6 и маркеров нейрональной дифференцировки в неокортексе и сетчатке плодов человека in vivo и in vitro. Клеточн. технол. биол. мед., 2009, № 4, с. 206-213.Гиляров А.В. Нестин в клетках центральной нервной системы. Морфология, 2007, т. 131, вып. 1, с. 85-90.Коржевский Д.Э., Гилерович Е.Г., Зинькова Н.Н. и др. Иммунохимическое выявление нейронов головного мозга с помощью селективного маркера NeuN. Морфология, 2005, т. 128, вып. 5, с. 76-78.Коржевский Д.Э. и Гиляров А.В. Иммуноцитохимическое выявление тканевых антигенов после длительного хранения объектов в метилсалицилате. Морфология, 2008, т. 134, вып. 6, с. 76-78.Коржевский Д.Э., Петрова Е.С., Кирик О.В. и др. Нейральные маркеры, используемые при изучении дифференцировки стволовых клеток. Клеточная трансплантология и тканевая инженерия, 2010, т. 5, № 3, с. 1-7.Коржевский Д.Э., Петрова Е.С., Кирик О.В. и Отеллин В.А. Оценка дифференцировки нейронов в эмбриогенезе крысы с использованием иммуноцитохимического выявления даблкортина. Морфология, 2008, т. 133, вып. 4, с. 7-10.Коржевский Д.Э., Хожай Л.И., Гилерович Е.Г. и др. Современные морфологические методы оценки деструктивных процессов, развивающихся в головном мозге в ответ на повреждающие воздействия. В кн.: Структурно-функциональные и нейрохимические закономерности асимметрии и пластичности мозга. М., ИЗПЦ «Информкнига», 2006, с. 139-142.Сосунов А.А. и Челышев Ю.А. Стволовая нервная клетка мозга. Успехи физиол. наук, 2002, т. 33, № 1, с. 17-28.Albala J.S., Kress Y., Liu W.K. et.al. Human microtubuleassociated protein-2c localizes to dendrites and axons in fetal spinal motor neurons. J. Neurochem., 1995, v. 64, № 6, p. 2480- 2490.Alexa A., Tompa P., Baki A. et al. Mutual protection of microtubuleassociated protein 2 (MAP2) and cyclic AMP-dependent protein kinase II against mu-calpain. J. Neurosci. Res., 1996, v. 44, № 5, p. 438-445.Alexander J.E., Hunt D.F., Lee M.K. et.al. Characterization of posttranslational modifications in neuron-specific class III betatubulin by mass spectrometry. Proc. Natl. Acad. Sci. USA, 1991, v. 88, № 11, p. 4685-4689.Avwenagha O., Campbell G. and Bird M.M. Distribution of GAP43, beta-III tubulin and F-actin in developing and regenerating axons and their growth cones in vitro, following neurotrophin treatment. J. Neurocytol., 2003, v. 32, № 9, p. 1077-1089.Bai J., Ramos R.L. and Ackman J.B. RNAi reveals doublecortin is required for radial migration in rat neocortex. Nat. Neurosci., 2003, v.6, № 12, p. 1277-1283.Banerjee A., Roach M.C., Trcka P. and Luduena R.F. Increased microtubule assembly in bovine brain tubulin lacking the type III isotype of beta-tubulin. J. Biol. Chem., 1990; v. 265, № 3, p.1794-1799.Binder L.I., Frankfurter A., Kim H. et.al. Heterogeneity of microtubule-associated protein 2 during rat brain development. Proc. Natl. Acad. Sci. USA, 1984, v. 81, № 17, p. 5613-5617.Bystron I., Rakic P., Molnar Z. and Blakemore C. The first neurons of the human cerebral cortex. Nat. Neurosci., 2006, v. 9, № 7, p. 880-886.Cunningham C.C., Leclerc N., Flanagan L.A. et.al. Microtubuleassociated protein 2c reorganizes both microtubules and microfilaments into distinct cytological structures in an actinbinding protein-280-deficient melanoma cell line. J. Cell Biol., 1997, v. 136, № 4, p. 845-857.Daou M.C., Smith T.W., Litofsky N.S. et.al. Doublecortin is preferentially expressed in invasive human brain tumors. Acta Neuropathol., 2005, v. 110, № 5, p. 472-480.De Wit M.C., Lequin M.H., de Coo I.F. et al. Cortical brain malformations: effect of clinical, neuroradiological, and modern genetic classification. Arch. Neurol., 2008, v. 65, № 3, p. 358-366.Dehmelt L.and Halpain S. Actin and microtubules in neurite initiation: are MAPs the missing link? J. Neurobiol., 2004, v. 58, № 1, p. 18-33.Dellarole A. and Grilli M. Adult dorsal root ganglia sensory neurons express the early neuronal fate marker doublecortin. J. Comp. Neurol., 2008, v. 511, № 3, p. 318-328.Dennis K., Uittenbogaard M., Chiaramello A. and Moody S.A. Cloning and characterization of the 5'-flanking region of the rat neuron-specific Class III beta-tubulin gene. Gene, 2002, v. 294, № 1-2, p. 269-277.Des Portes V., Pinard J.M., Billuart P. et.al. A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome. Cell, 1998, v. 92, № 1, p. 51-61.Deuel T.A., Liu J.S. and Corbo J.C. Genetic interaction between doublecortin and doublecortin-like kinase in neuronal migration and axon outgrowth. Neuron, 2006, v.49, № 1, p. 41-53.Dinsmore J.H. and Solomon F. Inhibition of MAP2 expression affects both morphological and cell division phenotypes of neuronal differentiation. Cell, 1991, v. 64, № 4, p. 817-826.Dráberová E., Del Valle L., Gordon J. et.al. Class III beta-tubulin is constitutively coexpressed with glial fibrillary acidic protein and nestin in midgestational human fetal astrocytes: implications for phenotypic identity. J. Neuropathol. Exp. Neurol., 2008, v. 67, № 4, p. 341-354.Fanarraga M.L., Avila J. and Zabala J.C. Expression of unphosphorylated class III beta-tubulin isotype in neuroepithelial cells demonstrates neuroblast commitment and differentiation. Eur. J. Neurosci., 1999; v. 11, № 2, p. 516-527.Farah C.A. and Leclerc N. HMWMAP2: new perspectives on a pathway to dendritic identity. Cell Motil. Cytoskeleton., 2008, v.65, № 7, p. 515-527.Farah C.A., Liazoghli D., Perreault S. et.al. Interaction of microtubule-associated protein-2 and p63: a new link between microtubules and rough endoplasmic reticulum membranes in neurons. J. Biol. Chem. , 2005, v. 280, № 10, p.9439-9449.Felgner H., Frank R., Biernat J. et.al. Domains of neuronal microtubule-associated proteins and flexural rigidity of microtubules. J. Cell Biol., 1997, v. 138, № 5, p. 1067-1075.Ferhat L., Represa A., Ferhat W. et.al. MAP2d mRNA is expressed in identified neuronal populations in the developing and adult rat brain and its subcellular distribution differs from that of MAP2b in hippocampal neurones. Eur. J. Neurosci., 1988, v.10, №1, p. 161-171.Folkerts M.M., Berman R.F., Muizelaar J.P. and Rafols J.A. Disruption of MAP-2 immunostaining in rat hippocampus after traumatic brain injury. J. Neurotrauma, 1998, v. 15, № 5, p. 349- 363.Friocourt G., Koulakoff A., Chafey P. et.al. Doublecortin functions at the extremities of growing neuronal processes. Cereb. Cortex, 2003, v. 13, № 6, p. 620-626.Friocourt G., Liu J.S., Antypa M. et al. Both doublecortin and doublecortin-like kinase play a role in cortical interneuron migration. J. Neurosci., 2007, v. 27, № 14, p. 3875-3883.Gonzalez-Perez O., Quinones-Hinojosa A. Dose-dependent effect of EGF on migration and differentiation of adult subventricular zone astrocytes. Glia, 2010, v. 58, № 8, p. 975-983.Graham M.E., Ruma-Haynes P., Capes-Davis A.G. et al. Multisite phosphorylation of doublecortin by cyclin-dependent kinase 5. Biochem. J., 2004, v. 381, Pt 2, p.471-481.Guo J., Walss-Bass C. and Ludueña R.F. The beta isotypes of tubulin in neuronal differentiation. Cytoskeleton (Hoboken), 2010, v. 67, № 7, p. 431-441.Hammond J.W., Cai D. and Verhey K.J. Tubulin modifications and their cellular functions. Curr. Opin. Cell Biol., 2008, v. 20, № 1, p. 71-76.Harada A., Teng J., Takei Y. et.al. MAP2 is required for dendrite elongation, PKA anchoring in dendrites, and proper PKA signal transduction. J. Cell Biol., 2002, v. 158, № 3, p. 541-549.Huh J.W., Raghupathi R., Laurer H.L.et.al. Transient loss of microtubule-associated protein 2 immunoreactivity after moderate brain injury in mice. J. Neurotrauma, 2003, v. 20, № 10, p. 975-984.Jiang Y.Q. and Oblinger M.M. Differential regulation of beta III and other tubulin genes during peripheral and central neuron development. J. Cell Sci., 1992, v. 103, Pt 3, p. 643-651.Kalcheva N., Rockwood J.M., Kress Y. et al. Molecular and functional characteristics of MAP-2a: ability of MAP-2a versus MAP-2b to induce stable microtubules in COS cells. Cell Motil. Cytoskeleton, 1998, v. 40, № 3, p. 272-285.Kappeler C., Saillour Y., Baudoin J.P. et.al. Branching and nucleokinesis defects in migrating interneurons derived from doublecortin knockout mice. Hum. Mol. Genet., 2006, v. 15, № 9, p. 1387-1400.Kerjan G., Koizumi H., Han E.B. et.al. Mice lacking doublecortin and doublecortin-like kinase 2 display altered hippocampal neuronal maturation and spontaneous seizures. Proc. Natl. Acad. Sci. USA., 2009, v. 106, № 16, p. 6766-6771.Khan I.A. and Luduena R.F. Phosphorylation of beta III-tubulin. Biochemistry, 1996, v. 35, № 12, p. 3704-3711.Kim M.H., Cierpicki T., Derewenda U. et al. The DCX-domain tandems of doublecortin and doublecortin-like kinase. Nat. Struct. Biol., 2003, v. 10, № 5, p. 324-333.Koizumi H., Tanaka T.and Gleeson J.G. Doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration. Neuron, 2006, v. 49, № 1, p. 55-66.Kozireski-Chuback D., Wu G. and Ledeen R.W. Upregulation of nuclear GM1 accompanies axon-like, but not dendrite-like, outgrowth in NG108-15 cells. J. Neurosci. Res., 1999, v. 55, № 1, p. 107-118.Kwei S.L., Clement A., Faissner A. and Brandt R. Differential interactions of MAP2, tau and MAP5 during axogenesis in culture. Neuroreport, 1998, v. 9, № 6, p. 1035-1040.Langnaese K., Seidenbecher C., Wex H. et.al. Protein components of a rat brain synaptic junctional protein preparation. Brain Res. Mol. Brain Res., 1996, v. 42, № 1, p. 118-122.Liu L., Geisert E.E., Frankfurter A. et al. A transgenic mouse class-III beta tubulin reporter using yellow fluorescent protein. Genesis, 2007, v. 45, № 9, p. 560-569.Lopez L.A. and Sheetz M.P. Steric inhibition of cytoplasmic dynein and kinesin motility by MAP2. Cell Motil. Cytoskeleton, 1993, v. 24, № 1, p. 1-16.Loveland K.L., Hayes T.M., Meinhardt A. et al. Microtubuleassociated protein-2 in the rat testis: a novel site of expression. Biol. Reprod., 1996, v. 54, № 4, p. 896-904.Ludueña RF. Multiple forms of tubulin: different gene products and covalent modifications. Int. Rev. Cytol., 1998, v. 178, p. 207-275.Matsunaga W., Miyata S. and Kiyohara T. Redistribution of MAP2 immunoreactivity in the neurohypophysial astrocytes of adult rats during dehydration. Brain Res., 1999, v. 829, № 1-2, p. 7-17.Messi E., Florian M.C., Caccia C. et al. Retinoic acid reduces human neuroblastoma cell migration and invasiveness: effects on DCX, LIS1, neurofilaments-68 and vimentin expression. BMC Cancer. 2008, v. 8, № 30, p. 1-12.Moores C.A., Perderiset M., Francis F. et.al. Mechanism of microtubule stabilization by doublecortin. Mol. Cell, 2004, v. 14, № 6, p. 833-839.Nacher J., Crespo C. and McEwen B.S. Doublecortin expression in the adult rat telencephalon. Eur. J. Neurosci., 2001, v. 14, № 4, p. 629-644.Nakagomi T., Taguchi A., Fujimori Y. et al Isolation and characterization of neural stem/progenitor cells from post-stroke cerebral cortex in mice. Eur. J. Neurosci., 2009, v. 29, № 9, p. 1842-1852Pietranera L., Lima A., Roig P. and De Nicola A.F. Involvement of brain-derived neurotrophic factor and neurogenesis in oestradiol neuroprotection of the hippocampus of hypertensive rats. J. Neuroendocrinol, 2010. v. 22, № 10, p. 1082-1092.Prajerova I., Honsa P., Chvatal A. and Anderova M. Neural stem/ progenitor cells derived from the embryonic dorsal telencephalon of D6/GFP mice differentiate primarily into neurons after transplantation into a cortical lesion. Cell Mol. Neurobiol., 2010, v. 30, № 2, p. 199-218.Ramos R.L., Bai J. and LoTurco J.J. Heterotopia formation in rat but not mouse neocortex after RNA interference knockdown of DCX. Cereb. Cortex, 2006, v. 16, № 9, p. 1323-1331.Reiner O., Coquelle F.M., Peter B. et al. The evolving doublecortin (DCX) superfamily. BMC Genomics, 2006, v. 7, № 188, p. 1-16.Rubino H.M., Dammerman M., Shafit-Zagardo B.and Erlichman J. Localization and characterization of the binding site for the regulatory subunit of type II cAMP-dependent protein kinase on MAP2. Neuron, 1989, v. 3, № 5, p. 631-638.Sánchez C., Díaz-Nido J. and Avila J. Phosphorylation of microtubule-associated protein 2 (MAP2) and its relevance for the regulation of the neuronal cytoskeleton function. Prog. Neurobiol., 2000, v. 61, № 2, p. 133-168.Sharma R.K. and Netland P.A. Early born lineage of retinal neurons express class III beta-tubulin isotype. Brain Res., 2007, v. 1176, p. 11-17.Shen Y. and Yu L.C. Potential protection of curcumin against hypoxia-induced decreases in beta-III tubulin content in rat prefrontal cortical neurons. Neurochem. Res., 2008, v. 33, № 10, p. 2112-2117.Shmueli A., Gdalyahu A., Sapoznik S. et.al. Site-specific dephosphorylation of doublecortin (DCX) by protein phosphatase 1 (PP1). Mol. Cell Neurosci., 2006, v. 32, № 1-2, p. 15-26.Skoda D., Kranda K., Bojar M. et al. Antibody formation against beta-tubulin class III in response to brain trauma. Brain Res. Bull., 2006, v. 68, № 4, p. 213-216.Sullivan K.F. Structure and utilization of tubulin isotypes. Annu. Rev. Cell Biol., 1988, v. 4, p. 687-716.Teng J., Takei Y., Harada A. et al. Synergistic effects of MAP2 and MAP1B knockout in neuronal migration, dendritic outgrowth, and microtubule organization. J. Cell Biol., 2001, v. 155, № 1, p. 65-76.Tucker R.P. and Matus A.I. Microtubule-associated proteins characteristic of embryonic brain are found in the adult mammalian retina. Dev. Biol., 1988, v. 130, № 2, p. 423-434.Valdivia M.M., Avila J., Coll J. et al. Quantitation and characterization of the microtubule associated MAP2 in porcine tissues and its isolation from porcine (PK15) and human (HeLa) cell lines. Biochem. Biophys. Res. Commun., 1982, v. 105, № 4, p. 1241-1249.Viereck C., Tucker R.P. and Matus A. The adult rat olfactory system expresses microtubule-associated proteins found in the developing brain. J. Neurosci., 1989, v. 9, № 10, p. 3547-3557.Yamanouchi H., Jay V., Otsubo H. et al. Early forms of microtubule-associated protein are strongly expressed in cortical dysplasia. Acta. Neuropathol., 1998, v. 95, № 5, p. 466-470.