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Mios在调节LIM Kinase对cofilin磷酸化中的 作用

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Name pinyin
XIA Shiyao
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0710 生物学
Subject category of dissertation
07 理学
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聚合形成丝状肌动蛋白(Actin Fliament, F-actin),是细胞骨架及肌肉收缩装置的
如细胞迁移,细胞分裂以及细胞的内吞作用等等。 过去的数十年中, F-actin 的动
我们发现了一个新的肌动蛋白调节因子 Mios,遗传研究表明, Mios 的敲除会导致
F-actin 的升高,说明 Mios 可能会影响肌动蛋白动力学。 本文的中心是利用生物化
学手段,研究 Mios 通过影响 LIM 激酶(LIM Kinase, LIMK) 对 cofilin 磷酸化这
肌动蛋白解聚因子(cofilin) 通过对加速肌动蛋白的解聚进而影响肌动蛋白的
动态调节, LIMK 可通过磷酸化 cofilin 进而抑制 cofilin 的活性,但影响磷酸化调
节水平的机制尚未明确。 基于肖老师在四川大学的课题组的发现, 在外周神经系
统中特异性敲除 Mios 会导致 F-actin 增加,磷酸化 cofilin 水平升高的现象,这表
明 Mios 的敲除影响了 cofilin 的磷酸化水平,进而影响了肌动蛋白动力学,但具体
Mios 蛋白作为 GATOR2 复合体的一个亚基,在 N 端含有一个 WD40 Repeat
Domain(WDR Domain)和一个在 C 端的锌带状结构域(Zinc Ribbon Domain)。
以往对于 Mios 的研究主要聚焦于 Mios 依赖 GATOR2 复合体对 mTORC1 信号通路
的调控以及 Mios 在细胞核内调控核基因的功能。本研究中,通过 GST pull-down、
激酶-底物反应以及肌动蛋白解聚试验, 发现了 Mios 在调控肌动蛋白的动态变化中
具有双重作用, 一方面可以抑制 LIMK 对 cofilin 的磷酸化,另一方面与 cofilin 结
合降低了 cofilin 解聚肌动蛋白的活性,并且 Mios 发挥这一功能既不依赖于 WDR
结构域,也不依赖于锌带状结构域,而是依赖于 Mios 中间的一段未知结构域。
Mios 蛋白这种新功能的发现为肌动蛋白动力学调节提供了新的分子模型,对了解

Other Abstract

Actin, as a globular protein, exists in almost all eukaryotic cells. Actin Fliation
(F-actin) is a basic component of the cytoskeleton and muscle contraction apparatus.
Many essential physiological processes in animal cells require actin dynamics, such as
cell migration, cell division and endocytosis. In the past decades, the dynamics of
F-actin has been the focus of research, which is still full of controversy and unknown. In
this paper, we found a new actin regulatory factor, Mios. Genetic studies show that the
knockout of Mios leads to an increase in F-actin, suggesting that Mios may affect actin
dynamics. This paper is focus on study the effect of Mios on the phosphorylation of
cofilin by LIM Kinase (LIMK) and actin dynamics by biochemical methods.
Actin dynamics plays an important role in myelination. Actin depolymerization
factor (cofilin) affects actin dynamic by accerlating the speed of actin depolymerization.
LIMK can inhibit the activity of cofilin by phosphorylating cofilin, but the mechanism
under LIMK affects the phosphorylation level of cofilin is still unknown. Based on
previous findings from Prof. Xiao’s Lab in Sichuan University, conditional knockout of
Mios in peripheral nervous system leads to an increase in F-actin and phosphorylated
cofilin levels, which indicates that the knockout of Mios affects the phosphorylation
level of cofilin and actin dynamics, but the specific mechanism is not yet clear.
As a component of GATOR2 complex, Mios protein contains a WD40 Repeat
Domain (WDR Domain) at N-terminal and a Zinc Ribbon Domainat at C-terminal.
Previous studies on Mios have focused on the regulation of mTORC1 signaling pathway
by GATOR2 complex and the function of regulating nuclear genes. In this study, GST
pull-down, kinase-substrate reaction and actin depolymerization experiments were used
to provide Mios with a new key function: regulating actin dynamic and myelination.
Results showed that Mios has dual roles in regulating actin dynamics: on the one hand,
it can inhibit the phosphorylation of cofilin by LIMK, on the other hand, it’s binding
with cofilin decreases the activity of cofilin depolymerization actin. The more important
is, this function depend neither on the WDR domain nor the Zinc Ribbon Domain, but
depend on an unknown domain in the middle of Mios. The discovery of the new
function of Mios provides a new molecular model for the regulation of actin dynamics,
which is of great significance for understanding acin dynamics.

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References List

[1] Laurent B, Rajaa B P, Cécile S, et al. Actin dynamics, architecture, and mechanics in cell motility[J].Physiological Reviews, 2014, 94(1): 235-63.
[2] Higgs H N. Discussing the morphology of actin filaments in lamellipodia[J]. Trends in Cell Biology,2011, 21(1): 2-4.
[3] R Dyche M. The instability of stabilization[J]. Proceedings of the National Academy of Sciences ofthe United States of America, 2012, 109(27): 10743-10744.
[4] Holmes K C, Popp D, ., Gebhard W, ., et al. Atomic model of the actin filament[J]. Nature, 1990,347(6288): 44-49.
[5] Sept D, Elcock A H, Mccammon J A. Computer simulations of actin polymerization can explain thebarbed-pointed end asymmetry 1[J]. Journal of Molecular Biology, 1999, 294(5): 1181-1189.
[6] Wegner A, Engel J. Kinetics of the cooperative association of actin to actin filament[J]. BiophysicalChemistry, 1975, 3(3): 215-225.
[7] Laurent B, Pollard T D. Hydrolysis of ATP by polymerized actin depends on the bound divalent cationbut not profilin[J]. Biochemistry, 2002, 41(2): 597-602.
[8] Blanchoin L, ., Pollard T D. Mechanism of interaction of Acanthamoeba actophorin (ADF/Cofilin)with actin filaments[J]. Journal of Biological Chemistry, 1999, 274(22): 15538-46.
[9] Pollard T D, Blanchoin L, Mullins R D. Molecular mechanisms controlling actin filament dynamics innonmuscle cells[J]. Annu.rev.biophys Biomol.struct, 2000, 29(1): 545.
[10] Pollard T D. Rate constants for the reactions of ATP- and ADP-actin with the ends of actinfilaments[J]. Journal of Cell Biology, 1986, 103(6): 2747-2754.
[11] Mullins R D, Stafford W F, Pollard T D. Structure, subunit topology, and actin-binding activity of theArp2/3 complex from Acanthamoeba[J]. Journal of Cell Biology, 1997, 136(2): 331-343.
[12] Robinson R C, Turbedsky K, ., Kaiser D A, et al. Crystal structure of Arp2/3 complex[J]. Science,2001, 294(5547): 1679-1684.
[13] Svitkina T M, Borisy G G. Arp2/3 complex and actin depolymerizing factor/cofilin in dendriticorganization and treadmilling of actin filament array in lamellipodia[J]. Journal of Cell Biology, 1999,145(5): 1009-1026.
[14] Weinberg J, Drubin D G. Clathrin-mediated endocytosis in budding yeast[J]. Trends in Cell Biology,2012, 22(1): 1-13.
[15] Kexi Y, Rong L. Actin cytoskeleton in cell polarity and asymmetric division during mouse oocytematuration[J]. Cell Motility & the Cytoskeleton, 2012, 69(10): 727-737.
[16] Frischknecht F, ., Moreau V, ., R?Ttger S, ., et al. Actin-based motility of vaccinia virus mimicsreceptor tyrosine kinase signalling[J]. Nature, 1999, 401(6756): 926.
[17] Cameron L A, Svitkina T M, Vignjevic D, et al. Dendritic organization of actin comet tails[J].Current Biology Cb, 2001, 11(2): 130-135.
[18] Hn H, Td P. Regulation of actin polymerization by Arp2/3 complex and WASp/Scar proteins[J]. TheJournal of biological chemistry, 1999, 274(46): 32531-32534.
[19] Achard V, Martiel J-L, Michelot A, et al. A "Primer"-Based Mechanism Underlies Branched ActinFilament Network Formation and Motility[J]. Current Biology: CB, 2010, 20(5): 423-428.
[20] C S, C W, Jv S, et al. Reply: Visualizing branched actin filaments in lamellipodia by electrontomography[J]. Nature cell biology, 2011, 13(9): 1013-1014.
[21] Rh. I, Lm. M. Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate theactincytoskeleton through the Arp2/3 complex[J]. Current Biology: CB, 1998, 8(25): 1347-1356.
[22] L B, Td P, Hn H, et al. Scar, a WASp-related protein, activates nucleation of actin filaments by theArp2/3 complex[J]. Proceedings of the National Academy of Sciences of the United States of America.,1999, 96(7): 3739-3744.
[23] Rotty J D, Wu C, Bear J E. New insights into the regulation and cellular functions of the ARP2/3complex[J]. Nature reviews: molecular cell biology, 2013, 14(1): 7-12.
[24] R D, Z G, F K, et al. Actin-bound structures of Wiskott-Aldrich syndrome protein(WASP)-homology domain 2 and the implications for filament assembly[J]. Proceedings of the NationalAcademy of Sciences of the United States of America., 2005, 102(46): 16644-16649.
[25] O A, Rd M. Capping protein increases the rate of actin-based motility by promoting filamentnucleation by the Arp2/3 complex[J]. Cell, 2008, 133(5): 841-851.
[26] A B-S, L H, Y B-K, et al. Reconstitution of the transition from lamellipodium to filopodium in amembrane-free system[J]. Proceedings of the National Academy of Sciences of the United States ofAmerica., 2006, 103(13): 4906-4911.
[27] Boujemaa-Paterski R, Manzi J, Sykes C, et al. How actin network dynamics control the onset ofactin-based motility[J]. Proceedings of the National Academy of Sciences of the United States ofAmerica., 2012, 109(36): 14440-14445.
[28] D P, R B, D D, et al. The Arp2/3 complex branches filament barbed ends: functional antagonism withcapping proteins[J]. Nature Cell Biology, 2000, 2(7).
[29] Cambier T, Reymann A-C, Martiel J-L. Nucleation geometry governs ordered actin networksstructures[J]. Nature materials, 2010, 9(10): 827-832.
[30] L B, J A K, N H H, et al. Direct observation of dendritic actin filament networks nucleated by Arp2/3complex and WASP/Scar proteins[J]. Nature, 2000, 404(6781).
[31] Leduc P, Guerin C, Galland R. Fabrication of three-dimensional electrical connections by means ofdirected actin self-organization[J]. Nature materials, 2013, 12(5): 416-421.
[32] Bamburg J R, Harris H E, Weeds A G. Partial purification and characterization of an actindepolymerizing factor from brain[J]. Febs Letters, 1980, 121(1): 178-182.
[33] Bernstein B W, Bamburg J R. ADF/Cofilin: a functional node in cell biology[J]. Trends in CellBiology, 2010, 20(4).
[34] Elena I, Ying H J, Dyche M R. Arp2/3 complex ATP hydrolysis promotes lamellipodial actin networkdisassembly but is dispensable for assembly[J]. The Journal of cell biology, 2013, 200(5).
[35] Anne-Cécile R, Cristian S, Christophe G, et al. Turnover of branched actin filament networks bystochastic fragmentation with ADF/cofilin[J]. Molecular Biology of the Cell (Online), 2011, 22(14).
[37] Anthony B, Kevin E, G F R. ERM proteins and merlin: integrators at the cell cortex[J]. NatureReviews. Molecular Cell Biology, 2002, 3(8).
[38] Chaudhry F, Breitsprecher D, Little K, et al. Srv2/cyclase-associated protein forms hexamericshurikens that directly catalyze actin filament severing by cofilin[J]. Molecular biology of the cell, 2013,24(1): 31-41.
[39] E A, Td P. Mechanism of actin filament turnover by severing and nucleation at differentconcentrations of ADF/cofilin[J]. Molecular cell, 2006, 24(1): 13-23.
[40] J A K, D P T. Direct real-time observation of actin filament branching mediated by Arp2/3 complexusing total internal reflection fluorescence microscopy[J]. PROCEEDINGS OF THE NATIONALACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98(26).
[41] Fujiwara I, Suetsugu S, Uemura S, et al. Visualization and force measurement of branching byArp2/3 complex and N-WASP in actin filament[J]. Biochemical and Biophysical ResearchCommunications, 2002, 293(5).
[42] Elam W A, Kang H, Cruz E M D L. Biophysics of actin filament severing by cofilin[J]. FEBSLetters, 2013, 587(8).
[43] R M B, Laurent B, Jean-Louis M, et al. Cofilin increases the bending flexibility of actin filaments:implications for severing and cell mechanics[J]. JMB Online, 2008, 381(3).
[44] I M. An actin-depolymerizing protein (depactin) from starfish oocytes: properties and interactionwith actin[J]. The Journal of Cell Biology, 1983, 97(5 Pt 1).
[45] Td P, L B. Mechanism of interaction of Acanthamoeba actophorin (ADF/Cofilin) with actinfilaments[J]. The Journal of biological chemistry, 1999, 274(22): 15538-15546.
[46] Suarez C, Roland J, Boujemaa-Paterski R, et al. Cofilin Tunes the Nucleotide State of ActinFilaments and Severs at Bare and Decorated Segment Boundaries[J]. Current Biology: CB, 2011, 21(10):862-868.
[47] C C, Cc B, Td P. Cofilin dissociates Arp2/3 complex and branches from actin filaments[J]. CurrentBiology: CB, 2009, 19(7): 537-545.
[48] Simone K, R B A. Contraction mechanisms in composite active actin networks[J]. PL o S One, 2012,7(7).
[49] Murrell M P, Gardel M L. F-actin buckling coordinates contractility and severing in a biomimeticactomyosin cortex[J]. Proceedings of the National Academy of Sciences of the United States of America.,2012, 109(51): 20820-20825.
[50] Ishikawa R, Sakamoto T, Ando T, et al. Polarized actin bundles formed by human fascin‐ 1: theirsliding and disassembly on myosin II and myosin V in vitro[J]. Journal of Neurochemistry, 2003, 87(3).
[51] Haviv L, Gillo D, Backouche F, et al. A Cytoskeletal Demolition Worker: Myosin II Acts as an ActinDepolymerization Agent[J]. Journal of Molecular Biology, 2008, 375(2).
[52] Blanchoin L, Martiel J-L, Cao W, et al. Actin Network Architecture Can Determine Myosin MotorActivity[J]. Science, 2012, 336(Jun.8 TN.6086): 1310-1314.
[53] Takako I, Lilly M A. missing oocyte encodes a highly conserved nuclear protein required for themaintenance of the meiotic cycle and oocyte identity in Drosophila[J]. Development, 2004, 131(5):1029-39.
[54] Bar-Peled L, Sabatini D M. A tumor suppressor complex with GAP activity for the RAG GTPasesthat signal amino acid sufficiency to mTORC1[J]. Science, 2013, 340(6136): 1100-1106.
[55] Chantranupong L, Scaria S, Saxton R, et al. The CASTOR Proteins Are Arginine Sensors for themTORC1 Pathway[J]. Cell, 2016, 165(1): 153-164.
[56] Schapira M, Tyers M, Torrent M, et al. WD40 repeat domain proteins: a novel target class?[J].Nature Reviews Drug Discovery, 2017, 16(11).
[57] Wolfe S A, Grant R A, Elrod-Erickson M, et al. Beyond the “Recognition Code” : Structures of TwoCys 2 His 2 Zinc Finger/TATA Box Complexes[J]. Structure, 2001, 9(8): 717-723.
[58] Laity J H, Lee B M, Wright P E. Zinc finger proteins: new insights into structural and functionaldiversity[J]. Current Opinion in Structural Biology, 2001, 11(1): 39-46.
[59] Leon O, Roth M. Zinc fingers: DNA binding and protein-protein interactions[J]. Biological Research,2000, 33(1): 21-30.
[60] Klug A, ., Schwabe J W. Protein motifs 5. Zinc fingers[J]. Faseb Journal, 1995, 9(8): 597.
[61] Krishna S S, Majumdar Igrishin N V. Structural classification of zinc fingers: survey and summary[J].Nucleic Acids Research, 2003, 31(2): 532-550.
[62] Maciver S K, Hussey P J. The ADF/cofilin family: actin-remodeling proteins[J]. Genome Biology,2002, 3(5): reviews3007.1.
[63] Loisel T P, Boujemaa R, ., Pantaloni D, ., et al. Reconstitution of actin-based motility of Listeria andShigella using pure proteins[J]. Nature, 1999, 401(6753): 613-616.
[64] Voytek O, Drubin D G. Cofilin recruitment and function during actin-mediated endocytosis dictatedby actin nucleotide state[J]. Journal of Cell Biology, 2007, 178(7): 1251-1264.
[65] Gian Carlo B, Gurniak C B, Emerald P, et al. N-cofilin is associated with neuronal migrationdisorders and cell cycle control in the cerebral cortex[J]. Genes & Development, 2007, 21(18):2347-2357.
[66] Gurniak C B, Emerald P, Walter W. The actin depolymerizing factor n-cofilin is essential for neuraltube morphogenesis and neural crest cell migration[J]. Developmental Biology, 2005, 278(1): 231-241.
[67] Satu K, Cristina C, Quentin M, et al. Actin depolymerizing factors cofilin1 and destrin are requiredfor ureteric bud branching morphogenesis[J]. Differentiation, 2010, 80(10): e1001176.
[68] Kanellos G, Zhou J, Patel H, et al. ADF and Cofilin1 Control Actin Stress Fibers, Nuclear Integrity,and Cell Survival[J]. Cell Reports, 2015, 13(9): 1949-1964.
[69] Weigang W, Robert E, John C. The cofilin pathway in breast cancer invasion and metastasis[J].Nature Reviews Cancer, 2007, 7(6): 429-440.
[70] Bamburg J R, Bernstein B W. Actin dynamics and cofilin-actin rods in Alzheimer disease[J].Cytoskeleton, 2016, 73(9): 477-497.
[71] Vartiainen M K, Mustonen T, Mattila P K, et al. The three mouse actin-depolymerizingfactor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics[J]. Molecular Biologyof the Cell, 2002, 13(1): 183-194.
[72] Yeoh S, Pope B, Mannherz H G, et al. Determining the differences in actin binding by human ADFand cofilin 1[J]. Journal of Molecular Biology, 2002, 315(4): 911-925.
[73] Gurniak C B, Perlas E, Witke W. The actin depolymerizing factor n-cofilin is essential for neuraltube morphogenesis and neural crest cell migration[J]. Developmental Biology, 2005, 278(1): 231-241.
[74] Chin S M, Jansen S, Goode B L. TIRF microscopy analysis of human Cof1, Cof2, and ADF effectson actin filament severing and turnover[J]. Journal of Molecular Biology, 2016, 428(8): 1604-1616.
[75] Zuchero J B, Fu M M, Sloan S A, et al. CNS myelin wrapping is driven by actin disassembly[J].Developmental Cell, 2015, 34(2): 152-167.
[76] Scott R W, Olson M F. LIM kinases: function, regulation and association with human disease[J].Journal of Molecular Medicine, 2007, 85(6): 555-568.
[77] Toshima J, Toshima J Y, Amano T, et al. Cofilin phosphorylation by protein kinase testicular proteinkinase 1 and its role in integrin-mediated actin reorganization and focal adhesion formation[J]. MolecularBiology of the Cell, 2001, 12(4): 1131.
[78] Ohashi K, ., Nagata K, ., Maekawa M, ., et al. Rho-associated kinase ROCK activates LIM-kinase 1by phosphorylation at threonine 508 within the activation loop[J]. Journal of Biological Chemistry, 2000,275(5): 3577.
[79] Miho K, Michiru N, Toshiaki M, et al. MAPKAPK-2-mediated LIM-kinase activation is critical forVEGF-induced actin remodeling and cell migration[J]. Embo Journal, 2014, 25(4): 713-726.
[80] Niwa R, Nagata-Ohashi K, Takeichi M, et al. Control of Actin Reorganization by Slingshot, a Familyof Phosphatases that Dephosphorylate ADF/Cofilin[J]. Cell, 2002, 108(2): 233-246.
[81] Antje G, J?Rg B, Bokoch G M. Chronophin, a novel HAD-type serine protein phosphatase, regulatescofilin-dependent actin dynamics[J]. Nature Cell Biology, 2005, 7(1): 21.
[82] Ambach A, Saunus J, Konstandin M, et al. The serine phosphatases PP1 and PP2A associate withand activate the actin-binding protein cofilin in human T lymphocytes[J]. European Journal ofImmunology, 2015, 30(12): 3422-3431.
[83] Zhao H, Hakala M, Lappalainen P. ADF/Cofilin Binds Phosphoinositides in a Multivalent Manner toAct as a PIP-Density Sensor[J]. Biophysical Journal, 2010, 98(10): 2327-2336.
[84] Ghassan M, Lilian S, Vera D M, et al. Phospholipase C and cofilin are required for carcinoma celldirectionality in response to EGF stimulation[J]. Journal of Cell Biology, 2004, 166(5): 697-708.
[85] Jacco V R, Xiaoyan S, Wies V R, et al. EGF-induced PIP2 hydrolysis releases and activates cofilinlocally in carcinoma cells[J]. Journal of Cell Biology, 2007, 179(6): 1247-1259.
[86] Xiaoyan S, Xiaoming C, Hideki Y, et al. Initiation of cofilin activity in response to EGF is uncoupledfrom cofilin phosphorylation and dephosphorylation in carcinoma cells[J]. Journal of Cell Science, 2006,119(14): 2871-81.
[87] Scott R W, Steven H, Diane C, et al. LIM kinases are required for invasive path generation by tumorand tumor-associated stromal cells[J]. Journal of Cell Biology, 2010, 191(1): 169-185.
[88] Kanellos G, Frame M C. Cellular functions of the ADF/cofilin family at a glance[J]. Journal of CellScience, 2016, 129(17): 3211.
[89] Christian F, Gabriela B, Laura D, et al. Cofilin is a pH sensor for actin free barbed end formation:role of phosphoinositide binding[J]. Journal of Cell Biology, 2008, 183(5): 865-879.
[90] Magalhaes M a O, Larson D R, Mader C C, et al. Cortactin phosphorylation regulates cell invasionthrough a pH-dependent pathway[J]. Journal of Cell Biology, 2011, 195(5): 903.
[91] Stanyon C A, Bernard O. LIM-kinase1[J]. International Journal of Biochemistry & Cell Biology,1999, 31(3-4): 389.
[92] Dan C, ., Kelly A, ., Bernard O, ., et al. Cytoskeletal changes regulated by the PAK4 serine/threoninekinase are mediated by LIM kinase 1 and cofilin[J]. Journal of Biological Chemistry, 2001, 276(34):32115-32121.
[93] Edwards D C, Gill G N. Structural features of LIM kinase that control effects on the actincytoskeleton[J]. Journal of Biological Chemistry, 1999, 274(16): 11352-61.
[94] Mezna M, Wong A C, Ainger M, et al. Development of a high-throughput screening method for LIMkinase 1 using a luciferase-based assay of ATP consumption[J]. Journal of Biomolecular Screening, 2012,17(4): 460-468.
[95] Agnew B J, Minamide L S, Bamburg J R. Reactivation of phosphorylated actin depolymerizingfactor and identification of the regulatory site[J]. Journal of Biological Chemistry, 1995, 270(29):17582-7.
[96] Ressad F, ., Didry D, ., Xia G X, et al. Kinetic analysis of the interaction of actin-depolymerizingfactor (ADF)/cofilin with G- and F-actins. Comparison of plant and human ADFs and effect ofphosphorylation[J]. Journal of Biological Chemistry, 1998, 273(33): 20894-20902.
[97] Hamill S, Lou H J, Turk B E, et al. Structural Basis for Noncanonical Substrate Recognition ofCofilin/ADF Proteins by LIM Kinases[J]. Molecular Cell, 2016, 62(3): 397-408.
[98] Goode B L, Sweeney M O, Eskin J A. GMF as an Actin Network Remodeling Factor[J]. Trends inCell Biology, 2018: S0962892418300722.
[99] Zuchero J B, Fu M M, Sloan S, et al. CNS Myelin Wrapping Is Driven by Actin Disassembly[J].Developmental Cell, 2015, 34(2): 152-167.

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夏诗尧. Mios在调节LIM Kinase对cofilin磷酸化中的 作用[D]. 哈尔滨. 哈尔滨工业大学,2019.
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