Home LiteratureArticle Details
PMID: 20066082 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Widely conserved signaling pathways in the establishment of cell polarity.

Cold Spring Harbor perspectives in biology ·Vol. 1 ·No. 2 ·2009-08-00 ·Pages a001370

McCaffrey LM, Macara IG

Abstract

How are the asymmetric distributions of proteins, lipids, and RNAs established and maintained in various cell types? Studies from diverse organisms show that Par proteins, GTPases, kinases, and phosphoinositides participate in conserved signaling pathways to establish and maintain cell polarity.

MeSH Terms
Animals Cell Lineage Cell Polarity Drosophila/metabolism GTP Phosphohydrolases/metabolism Humans Models, Biological Phenotype Protein Isoforms RNA, Messenger/metabolism Signal Transduction
Chemicals
Protein Isoforms RNA, Messenger GTP Phosphohydrolases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
McCaffrey Luke Martin
Department of Microbiology, Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908-5077, USA.
Macara Ian G
References (120)
120 references, click to expand
  1. Regulation of cell polarity and protrusion formation by targeting RhoA for degradation.
    Science. 2003 Dec 5;302(5651):1775-9 PMID: 14657501
  2. Structure of a cell polarity regulator, a complex between atypical PKC and Par6 PB1 domains.
    J Biol Chem. 2005 Mar 11;280(10):9653-61 PMID: 15590654
  3. Isoforms of the polarity protein par6 have distinct functions.
    J Biol Chem. 2004 Oct 1;279(40):41557-62 PMID: 15292221
  4. Sequential functioning of the ECT-2 RhoGEF, RHO-1 and CDC-42 establishes cell polarity in Caenorhabditis elegans embryos.
    Nat Cell Biol. 2006 Sep;8(9):978-85 PMID: 16921365
  5. PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1.
    Nat Cell Biol. 2005 Mar;7(3):270-7 PMID: 15723051
  6. Protein phosphatase 1 regulates the phosphorylation state of the polarity scaffold Par-3.
    Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10402-7 PMID: 18641122
  7. Cdc42: An essential Rho-type GTPase controlling eukaryotic cell polarity.
    Microbiol Mol Biol Rev. 1999 Mar;63(1):54-105 PMID: 10066831
  8. Polarization of the C. elegans embryo by RhoGAP-mediated exclusion of PAR-6 from cell contacts.
    Science. 2008 Jun 27;320(5884):1771-4 PMID: 18583611
  9. The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex.
    J Cell Biol. 2005 Sep 26;170(7):1029-37 PMID: 16186252
  10. Yeasts make their mark.
    Nat Cell Biol. 2003 Apr;5(4):294-9 PMID: 12669083
  11. Junctional adhesion molecule (JAM) binds to PAR-3: a possible mechanism for the recruitment of PAR-3 to tight junctions.
    J Cell Biol. 2001 Aug 6;154(3):491-7 PMID: 11489913
  12. Microtubules are involved in anterior-posterior axis formation in C. elegans embryos.
    J Cell Biol. 2007 Nov 5;179(3):397-402 PMID: 17967950
  13. Atypical protein kinase C cooperates with PAR-3 to establish embryonic polarity in Caenorhabditis elegans.
    Development. 1998 Sep;125(18):3607-14 PMID: 9716526
  14. Asymmetrically distributed PAR-3 protein contributes to cell polarity and spindle alignment in early C. elegans embryos.
    Cell. 1995 Dec 1;83(5):743-52 PMID: 8521491
  15. PATJ regulates tight junction formation and polarity in mammalian epithelial cells.
    J Cell Biol. 2005 Feb 28;168(5):705-11 PMID: 15738264
  16. Assembly of epithelial tight junctions is negatively regulated by Par6.
    Curr Biol. 2002 Feb 5;12(3):221-5 PMID: 11839275
  17. The Par3/aPKC interaction is essential for end bud remodeling and progenitor differentiation during mammary gland morphogenesis.
    Genes Dev. 2009 Jun 15;23(12):1450-60 PMID: 19528321
  18. Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts.
    J Cell Biol. 2000 Sep 18;150(6):1361-74 PMID: 10995441
  19. Par-3 mediates the inhibition of LIM kinase 2 to regulate cofilin phosphorylation and tight junction assembly.
    J Cell Biol. 2006 Feb 27;172(5):671-8 PMID: 16505165
  20. PIP5K-dependent production of PIP2 sustains microtubule organization to establish polarized transport in the Drosophila oocyte.
    Development. 2008 Dec;135(23):3829-38 PMID: 18948416
  21. PAR-6 regulates aPKC activity in a novel way and mediates cell-cell contact-induced formation of the epithelial junctional complex.
    Genes Cells. 2001 Aug;6(8):721-31 PMID: 11532031
  22. Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity.
    Science. 2005 Mar 11;307(5715):1603-9 PMID: 15761148
  23. RhoA, Rac1, and Cdc42 exert distinct effects on epithelial barrier via selective structural and biochemical modulation of junctional proteins and F-actin.
    Am J Physiol Cell Physiol. 2004 Aug;287(2):C327-35 PMID: 15044152
  24. Direct interaction of two polarity complexes implicated in epithelial tight junction assembly.
    Nat Cell Biol. 2003 Feb;5(2):137-42 PMID: 12545177
  25. The Caenorhabditis elegans par-5 gene encodes a 14-3-3 protein required for cellular asymmetry in the early embryo.
    Dev Biol. 2002 Jan 1;241(1):47-58 PMID: 11784094
  26. Drosophila PAR-1 and 14-3-3 inhibit Bazooka/PAR-3 to establish complementary cortical domains in polarized cells.
    Cell. 2003 Dec 12;115(6):691-704 PMID: 14675534
  27. par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed.
    Cell. 1995 May 19;81(4):611-20 PMID: 7758115
  28. Direct binding of cell polarity protein PAR-3 to cell-cell adhesion molecule nectin at neuroepithelial cells of developing mouse.
    J Biol Chem. 2003 Feb 21;278(8):5497-500 PMID: 12515806
  29. PAR3 is essential for cyst-mediated epicardial development by establishing apical cortical domains.
    Development. 2006 Apr;133(7):1389-98 PMID: 16510507
  30. Polarity complex proteins.
    Biochim Biophys Acta. 2008 Mar;1778(3):614-30 PMID: 18005931
  31. The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis.
    Nat Cell Biol. 2006 Mar;8(3):227-37 PMID: 16474385
  32. Symmetry breaking in the life cycle of the budding yeast.
    Cold Spring Harb Perspect Biol. 2009 Sep;1(3):a003384 PMID: 20066112
  33. PAR-6 is a conserved PDZ domain-containing protein that colocalizes with PAR-3 in Caenorhabditis elegans embryos.
    Development. 1999 Jan;126(1):127-35 PMID: 9834192
  34. Activation of the protein kinase Akt/PKB by the formation of E-cadherin-mediated cell-cell junctions. Evidence for the association of phosphatidylinositol 3-kinase with the E-cadherin adhesion complex.
    J Biol Chem. 1999 Jul 2;274(27):19347-51 PMID: 10383446
  35. The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42.
    Nat Cell Biol. 2000 Aug;2(8):531-9 PMID: 10934474
  36. Eukaryotic chemotaxis: distinctions between directional sensing and polarization.
    J Biol Chem. 2003 Jun 6;278(23):20445-8 PMID: 12672811
  37. The positioning and segregation of apical cues during epithelial polarity establishment in Drosophila.
    J Cell Biol. 2005 Aug 29;170(5):813-23 PMID: 16129788
  38. Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity.
    Cell. 2003 Jan 10;112(1):63-75 PMID: 12526794
  39. The polarity-inducing kinase Par-1 controls Xenopus gastrulation in cooperation with 14-3-3 and aPKC.
    EMBO J. 2004 Oct 27;23(21):4190-201 PMID: 15343271
  40. Par-3-mediated junctional localization of the lipid phosphatase PTEN is required for cell polarity establishment.
    J Biol Chem. 2008 Aug 22;283(34):23440-9 PMID: 18550519
  41. Regulated and polarized PtdIns(3,4,5)P3 accumulation is essential for apical membrane morphogenesis in photoreceptor epithelial cells.
    Curr Biol. 2006 Jan 24;16(2):140-9 PMID: 16431366
  42. Par3/Par6 polarity complex coordinates apical ectoplasmic specialization and blood-testis barrier restructuring during spermatogenesis.
    Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9657-62 PMID: 18621709
  43. Rho-kinase phosphorylates PAR-3 and disrupts PAR complex formation.
    Dev Cell. 2008 Feb;14(2):205-15 PMID: 18267089
  44. PTEN-mediated apical segregation of phosphoinositides controls epithelial morphogenesis through Cdc42.
    Cell. 2007 Jan 26;128(2):383-97 PMID: 17254974
  45. Membrane organization and dynamics in cell polarity.
    Cold Spring Harb Perspect Biol. 2009 Nov;1(5):a001321 PMID: 20066116
  46. Cell polarity and the cytoskeleton in the Caenorhabditis elegans zygote.
    Annu Rev Genet. 2003;37:221-49 PMID: 14616061
  47. The Maguk protein, Pals1, functions as an adapter, linking mammalian homologues of Crumbs and Discs Lost.
    J Cell Biol. 2002 Apr 1;157(1):161-72 PMID: 11927608
  48. Phosphorylation of the Par-1 polarity kinase by protein kinase D regulates 14-3-3 binding and membrane association.
    Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18378-83 PMID: 19011111
  49. Spontaneous cell polarization through actomyosin-based delivery of the Cdc42 GTPase.
    Science. 2003 Feb 21;299(5610):1231-5 PMID: 12560471
  50. PAR-1 is a Dishevelled-associated kinase and a positive regulator of Wnt signalling.
    Nat Cell Biol. 2001 Jul;3(7):628-36 PMID: 11433294
  51. XGAP, an ArfGAP, is required for polarized localization of PAR proteins and cell polarity in Xenopus gastrulation.
    Dev Cell. 2006 Jul;11(1):69-79 PMID: 16824954
  52. Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control.
    Nat Cell Biol. 2006 Nov;8(11):1235-45 PMID: 17060907
  53. Functions of the novel RhoGAP proteins RGA-3 and RGA-4 in the germ line and in the early embryo of C. elegans.
    Development. 2007 Oct;134(19):3495-505 PMID: 17728351
  54. The PAR proteins: fundamental players in animal cell polarization.
    Dev Cell. 2007 Nov;13(5):609-622 PMID: 17981131
  55. Cdc42 and noncanonical Wnt signal transduction pathways cooperate to promote cell polarity.
    J Cell Biol. 2007 Jul 30;178(3):355-61 PMID: 17646398
  56. Polarization of Drosophila neuroblasts during asymmetric division.
    Cold Spring Harb Perspect Biol. 2009 Aug;1(2):a001388 PMID: 20066083
  57. An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3.
    J Cell Biol. 1998 Oct 5;143(1):95-106 PMID: 9763423
  58. Inhibition of Rac by the GAP activity of centralspindlin is essential for cytokinesis.
    Science. 2008 Dec 5;322(5907):1543-6 PMID: 19056985
  59. Feedback signaling controls leading-edge formation during chemotaxis.
    Curr Opin Genet Dev. 2006 Aug;16(4):339-47 PMID: 16806895
  60. Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3.
    Dev Cell. 2007 Jul;13(1):15-28 PMID: 17609107
  61. Cortical flows powered by asymmetrical contraction transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo.
    Dev Cell. 2004 Sep;7(3):413-24 PMID: 15363415
  62. Cellular symmetry breaking during Caenorhabditis elegans development.
    Cold Spring Harb Perspect Biol. 2009 Oct;1(4):a003400 PMID: 20066102
  63. The polarity protein Par-3 directly interacts with p75NTR to regulate myelination.
    Science. 2006 Nov 3;314(5800):832-6 PMID: 17082460
  64. Self-association of PAR-3-mediated by the conserved N-terminal domain contributes to the development of epithelial tight junctions.
    J Biol Chem. 2003 Aug 15;278(33):31240-50 PMID: 12756256
  65. The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl.
    Nature. 2003 Mar 20;422(6929):326-30 PMID: 12629552
  66. A positive feedback loop stabilizes the guanine-nucleotide exchange factor Cdc24 at sites of polarization.
    EMBO J. 2002 Apr 2;21(7):1565-76 PMID: 11927541
  67. Structure of Cdc42 in a complex with the GTPase-binding domain of the cell polarity protein, Par6.
    EMBO J. 2003 Mar 3;22(5):1125-33 PMID: 12606577
  68. Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1.
    J Biol Chem. 2000 Sep 8;275(36):27979-88 PMID: 10856295
  69. Role of nectin in organization of tight junctions in epithelial cells.
    Genes Cells. 2002 Oct;7(10):1059-72 PMID: 12354099
  70. Regulated protein-protein interaction between aPKC and PAR-3 plays an essential role in the polarization of epithelial cells.
    Genes Cells. 2002 Nov;7(11):1161-71 PMID: 12390250
  71. Mechanisms of asymmetric stem cell division.
    Cell. 2008 Feb 22;132(4):583-97 PMID: 18295577
  72. The Par-Tiam1 complex controls persistent migration by stabilizing microtubule-dependent front-rear polarity.
    Curr Biol. 2007 Oct 9;17(19):1623-34 PMID: 17825562
  73. The Rho GTPase-activating proteins RGA-3 and RGA-4 are required to set the initial size of PAR domains in Caenorhabditis elegans one-cell embryos.
    Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):14976-81 PMID: 17848508
  74. Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling.
    EMBO J. 2006 Nov 1;25(21):5058-70 PMID: 17053785
  75. Distinct PAR-1 proteins function in different branches of Wnt signaling during vertebrate development.
    Dev Cell. 2005 Jun;8(6):829-41 PMID: 15935773
  76. Mechanisms of asymmetric cell division: flies and worms pave the way.
    Nat Rev Mol Cell Biol. 2008 May;9(5):355-66 PMID: 18431399
  77. Dynein regulates epithelial polarity and the apical localization of stardust A mRNA.
    PLoS Genet. 2008 Jan;4(1):e8 PMID: 18208331
  78. Dynein-mediated apical localization of crumbs transcripts is required for Crumbs activity in epithelial polarity.
    J Cell Biol. 2008 Jan 14;180(1):31-8 PMID: 18195099
  79. Planar cell polarity signaling: the developing cell's compass.
    Cold Spring Harb Perspect Biol. 2009 Sep;1(3):a002964 PMID: 20066108
  80. par-2, a gene required for blastomere asymmetry in Caenorhabditis elegans, encodes zinc-finger and ATP-binding motifs.
    Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6108-12 PMID: 8016123
  81. Linking cell cycle to asymmetric division: Aurora-A phosphorylates the Par complex to regulate Numb localization.
    Cell. 2008 Oct 3;135(1):161-73 PMID: 18854163
  82. PIP3 is involved in neuronal polarization and axon formation.
    J Neurochem. 2004 Apr;89(1):109-18 PMID: 15030394
  83. A conserved oligomerization domain in drosophila Bazooka/PAR-3 is important for apical localization and epithelial polarity.
    Curr Biol. 2003 Aug 5;13(15):1330-4 PMID: 12906794
  84. A casein kinase 1 and PAR proteins regulate asymmetry of a PIP(2) synthesis enzyme for asymmetric spindle positioning.
    Dev Cell. 2008 Aug;15(2):198-208 PMID: 18694560
  85. PDZ domains of Par-3 as potential phosphoinositide signaling integrators.
    Mol Cell. 2007 Dec 14;28(5):886-98 PMID: 18082612
  86. Identification of genes required for cytoplasmic localization in early C. elegans embryos.
    Cell. 1988 Feb 12;52(3):311-20 PMID: 3345562
  87. aPKC phosphorylates Miranda to polarize fate determinants during neuroblast asymmetric cell division.
    Curr Biol. 2009 May 12;19(9):723-9 PMID: 19375318
  88. CYK-4/GAP provides a localized cue to initiate anteroposterior polarity upon fertilization.
    Science. 2006 Sep 1;313(5791):1298-301 PMID: 16873611
  89. Interaction between PAR-3 and the aPKC-PAR-6 complex is indispensable for apical domain development of epithelial cells.
    J Cell Sci. 2009 May 15;122(Pt 10):1595-606 PMID: 19401335
  90. A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity.
    Nat Cell Biol. 2000 Aug;2(8):540-7 PMID: 10934475
  91. Interaction of PAR-6 with CDC-42 is required for maintenance but not establishment of PAR asymmetry in C. elegans.
    Dev Biol. 2006 Nov 15;299(2):386-97 PMID: 16996049
  92. Cytoskeletal mechanisms for breaking cellular symmetry.
    Cold Spring Harb Perspect Biol. 2010 Jan;2(1):a003392 PMID: 20182610
  93. Planar cell polarity signaling: from fly development to human disease.
    Annu Rev Genet. 2008;42:517-40 PMID: 18710302
  94. Phosphatidylinositol-3,4,5-trisphosphate regulates the formation of the basolateral plasma membrane in epithelial cells.
    Nat Cell Biol. 2006 Sep;8(9):963-70 PMID: 16921364
  95. Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity.
    Curr Biol. 2004 Apr 20;14(8):736-41 PMID: 15084291
  96. Quantitative analysis of protein dynamics during asymmetric cell division.
    Curr Biol. 2005 Oct 25;15(20):1847-54 PMID: 16243032
  97. The apical determinants aPKC and dPatj regulate Frizzled-dependent planar cell polarity in the Drosophila eye.
    Cell. 2005 May 20;121(4):621-631 PMID: 15907474
  98. PAR proteins and the cytoskeleton: a marriage of equals.
    Curr Opin Cell Biol. 2006 Feb;18(1):86-94 PMID: 16364625
  99. The C. elegans par-4 gene encodes a putative serine-threonine kinase required for establishing embryonic asymmetry.
    Development. 2000 Apr;127(7):1467-75 PMID: 10704392
  100. Loss of PALS1 expression leads to tight junction and polarity defects.
    Mol Biol Cell. 2004 Apr;15(4):1981-90 PMID: 14718565
  101. Remodeling epithelial cell organization: transitions between front-rear and apical-basal polarity.
    Cold Spring Harb Perspect Biol. 2009 Jul;1(1):a000513 PMID: 20066074
  102. The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase.
    Dev Cell. 2008 Feb;14(2):216-26 PMID: 18267090
  103. Multiple splice variants of Par3 and of a novel related gene, Par3L, produce proteins with different binding properties.
    Gene. 2002 Jul 10;294(1-2):99-107 PMID: 12234671
  104. The Crumbs3-Pals1 complex participates in the establishment of polarity in mammalian epithelial cells.
    J Cell Sci. 2003 Jul 15;116(Pt 14):2895-906 PMID: 12771187
  105. Dap160/intersectin binds and activates aPKC to regulate cell polarity and cell cycle progression.
    Development. 2008 Aug;135(16):2739-46 PMID: 18614576
  106. Echinoid is a component of adherens junctions that cooperates with DE-Cadherin to mediate cell adhesion.
    Dev Cell. 2005 Apr;8(4):493-504 PMID: 15809032
  107. The Par-3 NTD adopts a PB1-like structure required for Par-3 oligomerization and membrane localization.
    EMBO J. 2007 Jun 6;26(11):2786-96 PMID: 17476308
  108. Par-3 controls tight junction assembly through the Rac exchange factor Tiam1.
    Nat Cell Biol. 2005 Mar;7(3):262-9 PMID: 15723052
  109. Phosphorylation-dependent binding of 14-3-3 to the polarity protein Par3 regulates cell polarity in mammalian epithelia.
    Curr Biol. 2003 Dec 2;13(23):2082-90 PMID: 14653998
  110. aPKC-mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb.
    EMBO J. 2007 Jan 24;26(2):468-80 PMID: 17203073
  111. Regulation of neurocoel morphogenesis by Pard6 gamma b.
    Dev Biol. 2008 Dec 1;324(1):41-54 PMID: 18817769
  112. Regulation of cell polarity during epithelial morphogenesis.
    Curr Opin Cell Biol. 2008 Apr;20(2):227-34 PMID: 18282696
  113. Moving messages: the intracellular localization of mRNAs.
    Nat Rev Mol Cell Biol. 2005 May;6(5):363-75 PMID: 15852043
  114. Dishevelled promotes axon differentiation by regulating atypical protein kinase C.
    Nat Cell Biol. 2007 Jul;9(7):743-54 PMID: 17558396
  115. EphrinB1 controls cell-cell junctions through the Par polarity complex.
    Nat Cell Biol. 2008 Aug;10(8):979-86 PMID: 18604196
  116. Polarity and differential inheritance--universal attributes of life?
    Cell. 2008 Nov 28;135(5):801-12 PMID: 19041746
  117. Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity.
    Nat Cell Biol. 2004 Apr;6(4):328-34 PMID: 15048131
  118. APC and GSK-3beta are involved in mPar3 targeting to the nascent axon and establishment of neuronal polarity.
    Curr Biol. 2004 Nov 23;14(22):2025-32 PMID: 15556865
  119. Role of Lgl/Dlg/Scribble in the regulation of epithelial junction, polarity and growth.
    Front Biosci. 2008 May 01;13:6693-707 PMID: 18508688
  120. Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6 aPKC.
    J Cell Sci. 2007 Sep 15;120(Pt 18):3200-6 PMID: 17726059
Article Info
Journal
Cold Spring Harbor perspectives in biology
Abbr.
Cold Spring Harb Perspect Biol
ISSN
1943-0264
DOI
10.1101/cshperspect.a001370
Published
2009-08-00
Pages
a001370
Language
English
Region
United States
NLM ID
101513680
PMCID
PMC2742088
Subset
IM
Grants
NIGMS NIH HHS · R01 GM070902 · United States
CIHR · Canada
NIGMS NIH HHS · GM090702 · United States
External Links
PubMed source DOI: 10.1101/cshperspect.a001370 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2