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Volumn 161, Issue 5, 2003, Pages 979-989

Neuroglian, Gliotactin, and the Na+/k+ ATPase are essential for septate junction function in Drosophila

Author keywords

Epithelia; Glia; Na pump; Paracellular barrier; Paranodal septate junction

Indexed keywords

ADENOSINE TRIPHOSPHATASE (POTASSIUM SODIUM); ADENOSINE TRIPHOSPHATASE (POTASSIUM); GLIOTACTIN; MEMBRANE PROTEIN; NEUREXIN; NEUROGLIAN; UNCLASSIFIED DRUG;

EID: 0038457822     PISSN: 00219525     EISSN: None     Source Type: Journal    
DOI: 10.1083/jcb.200212054     Document Type: Article
Times cited : (198)

References (52)
  • 1
    • 0023222704 scopus 로고
    • The distribution of (Na+/K+)ATPase is continuous along the axolemma of unensheathed axons from spinal roots of 'dystrophic' mice
    • Ariyasu, R.G., and M.H. Ellisman. 1987. The distribution of (Na+/K+)ATPase is continuous along the axolemma of unensheathed axons from spinal roots of 'dystrophic' mice. J. Neurocytol. 16:239-248.
    • (1987) J. Neurocytol. , vol.16 , pp. 239-248
    • Ariyasu, R.G.1    Ellisman, M.H.2
  • 2
    • 0034065232 scopus 로고    scopus 로고
    • On the molecular architecture of myelinated fibers
    • Arroyo, E.J., and S.S. Scherer. 2000. On the molecular architecture of myelinated fibers. Histochem. Cell Biol. 113:1-18.
    • (2000) Histochem. Cell Biol. , vol.113 , pp. 1-18
    • Arroyo, E.J.1    Scherer, S.S.2
  • 3
    • 0029055716 scopus 로고
    • Gliotactin, a novel transmembrane protein on peripheral glia, is required to form the blood-nerve barrier in Drosophila
    • Auld, V.J., R.D. Fetter, K. Broadie, and C.S. Goodman. 1995. Gliotactin, a novel transmembrane protein on peripheral glia, is required to form the blood-nerve barrier in Drosophila. Cell. 81:757-767.
    • (1995) Cell , vol.81 , pp. 757-767
    • Auld, V.J.1    Fetter, R.D.2    Broadie, K.3    Goodman, C.S.4
  • 4
    • 0035499331 scopus 로고    scopus 로고
    • Posterior midgut epithelial cells differ in their organization of the membrane skeleton from other Drosophila epithelia
    • Baumann, O. 2001. Posterior midgut epithelial cells differ in their organization of the membrane skeleton from other Drosophila epithelia. Exp. Cell Res. 270: 176-187.
    • (2001) Exp. Cell Res. , vol.270 , pp. 176-187
    • Baumann, O.1
  • 6
    • 0033582916 scopus 로고    scopus 로고
    • Discs Lost, a novel multi-PDZ domain protein, establishes and maintains epithelial polarity
    • Bhat, M.A., S. Izaddoost, Y. Lu, K.O. Cho, K.W. Choi, and H.J. Bellen. 1999. Discs Lost, a novel multi-PDZ domain protein, establishes and maintains epithelial polarity. Cell 96:833-845.
    • (1999) Cell , vol.96 , pp. 833-845
    • Bhat, M.A.1    Izaddoost, S.2    Lu, Y.3    Cho, K.O.4    Choi, K.W.5    Bellen, H.J.6
  • 7
    • 0024358833 scopus 로고
    • Drosophila neuroglian: A member of the immunoglobulin superfamily with extensive homology to the vertebrate neural adhesion molecule L1
    • Bieber, A.J., P.M. Snow, M. Hortsch, N.H. Patel, J.R. Jacobs, Z.R. Traquina, J. Schilling, and C.S. Goodman. 1989. Drosophila neuroglian: a member of the immunoglobulin superfamily with extensive homology to the vertebrate neural adhesion molecule L1. Cell. 59:447-460.
    • (1989) Cell , vol.59 , pp. 447-460
    • Bieber, A.J.1    Snow, P.M.2    Hortsch, M.3    Patel, N.H.4    Jacobs, J.R.5    Traquina, Z.R.6    Schilling, J.7    Goodman, C.S.8
  • 8
    • 0034617129 scopus 로고    scopus 로고
    • Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors
    • Bilder, D., M. Li, and N. Perrimon. 2000. Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science. 289:113-116.
    • (2000) Science , vol.289 , pp. 113-116
    • Bilder, D.1    Li, M.2    Perrimon, N.3
  • 11
    • 0027999616 scopus 로고
    • Ankyrin binding activity shared by the neurofascin/L1/NrCAM family of nervous system cell adhesion molecules
    • Davis, J.Q., and V. Bennett. 1994. Ankyrin binding activity shared by the neurofascin/L1/NrCAM family of nervous system cell adhesion molecules. J. Biol. Chem. 269:27163-27166.
    • (1994) J. Biol. Chem. , vol.269 , pp. 27163-27166
    • Davis, J.Q.1    Bennett, V.2
  • 12
    • 0029899939 scopus 로고    scopus 로고
    • Neuroglian-mediated cell adhesion induces assembly of the membrane skeleton at cell contact sites
    • Dubreuil, R.R., G. MacVicar, S. Dissanayake, C. Liu, D. Homer, and M. Hortsch. 1996. Neuroglian-mediated cell adhesion induces assembly of the membrane skeleton at cell contact sites. J. Cell Biol. 133:647-655.
    • (1996) J. Cell Biol. , vol.133 , pp. 647-655
    • Dubreuil, R.R.1    MacVicar, G.2    Dissanayake, S.3    Liu, C.4    Homer, D.5    Hortsch, M.6
  • 13
    • 0030758350 scopus 로고    scopus 로고
    • Segregation of two spectrin isoforms: Polarized membrane-binding sites direct polarized membrane skeleton assembly
    • Dubreuil, R.R., P.B. Maddux, T.A. Grushko, and G.R. MacVicar. 1997. Segregation of two spectrin isoforms: polarized membrane-binding sites direct polarized membrane skeleton assembly. Mol. Biol. Cell. 8:1933-1942.
    • (1997) Mol. Biol. Cell , vol.8 , pp. 1933-1942
    • Dubreuil, R.R.1    Maddux, P.B.2    Grushko, T.A.3    MacVicar, G.R.4
  • 14
    • 0034192541 scopus 로고    scopus 로고
    • Drosophila β-spectrin functions independently of α-spectrin to polarize the Na, K ATP-ase in epithelial cells
    • Dubreuil, R.R., P. Wang, S. Dahl, J. Lee, and L.S. Goldstein. 2000. Drosophila β-spectrin functions independently of α-spectrin to polarize the Na, K ATP-ase in epithelial cells. J. Cell Biol. 149:647-656.
    • (2000) J. Cell Biol. , vol.149 , pp. 647-656
    • Dubreuil, R.R.1    Wang, P.2    Dahl, S.3    Lee, J.4    Goldstein, L.S.5
  • 15
    • 0031453392 scopus 로고    scopus 로고
    • The axonal membrane protein Caspr, a homologue of Neurexin IV, is a component of the septate-like paranodal junctions that assemble during myelination
    • Einheber, S., G. Zanazzi, W. Ching, S. Scherer, T.A. Milner, E. Peles, and J.L. Salzer. 1997. The axonal membrane protein Caspr, a homologue of Neurexin IV, is a component of the septate-like paranodal junctions that assemble during myelination. J. Cell Biol. 139:1495-1506.
    • (1997) J. Cell Biol. , vol.139 , pp. 1495-1506
    • Einheber, S.1    Zanazzi, G.2    Ching, W.3    Scherer, S.4    Milner, T.A.5    Peles, E.6    Salzer, J.L.7
  • 16
    • 0034524488 scopus 로고    scopus 로고
    • Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin
    • Fasano, A. 2000. Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Ann. NY Acad. Sci. 915:214-222.
    • (2000) Ann. NY Acad. Sci. , vol.915 , pp. 214-222
    • Fasano, A.1
  • 17
    • 0025849162 scopus 로고
    • Complex cellular and subcellular regulation of Notch expression during embryonic and imaginal development of Drosophila: Implications for Notch function
    • Fehon, R.G., K. Johansen, I. Rebay, and S. Artavanis-Tsakonas. 1991. Complex cellular and subcellular regulation of Notch expression during embryonic and imaginal development of Drosophila: implications for Notch function. J. Cell Biol. 113:657-669.
    • (1991) J. Cell Biol. , vol.113 , pp. 657-669
    • Fehon, R.G.1    Johansen, K.2    Rebay, I.3    Artavanis-Tsakonas, S.4
  • 18
    • 0028325048 scopus 로고
    • A Drosophila homologue of membrane-skeleton protein 4.1 is associated with septate junctions and is encoded by the coracle gene
    • Fehon, R.G., I.A. Dawson, and S. Artavanis-Tsakonas. 1994. A Drosophila homologue of membrane-skeleton protein 4.1 is associated with septate junctions and is encoded by the coracle gene. Development. 120:545-557.
    • (1994) Development , vol.120 , pp. 545-557
    • Fehon, R.G.1    Dawson, I.A.2    Artavanis-Tsakonas, S.3
  • 19
    • 0031108125 scopus 로고    scopus 로고
    • The Drosophila Na, K-ATPase α-subunit gene: Gene structure, promoter function and analysis of a cold-sensitive recessive-lethal mutation
    • Feng, Y., L. Huynh, K. Takeyasu, and D.M. Fambrough. 1997. The Drosophila Na, K-ATPase α-subunit gene: gene structure, promoter function and analysis of a cold-sensitive recessive-lethal mutation. Genes Funct. 1:99-117.
    • (1997) Genes Funct. , vol.1 , pp. 99-117
    • Feng, Y.1    Huynh, L.2    Takeyasu, K.3    Fambrough, D.M.4
  • 20
    • 0036316397 scopus 로고    scopus 로고
    • Endothelial barriers: From hypothetical pores to membrane proteins
    • Firth, J.A. 2002. Endothelial barriers: from hypothetical pores to membrane proteins. J Anat. 200:541-548.
    • (2002) J. Anat. , vol.200 , pp. 541-548
    • Firth, J.A.1
  • 21
    • 9044227627 scopus 로고    scopus 로고
    • FlyBase: The Drosophila database
    • FlyBase. 1996. FlyBase: the Drosophila database. Nucleic Acids Res. 24:53-56.
    • (1996) Nucleic Acids Res , vol.24 , pp. 53-56
  • 22
    • 0034525271 scopus 로고    scopus 로고
    • The EGF and FGF receptors mediate neuroglian function to control growth cone decisions during sensory axon guidance in Drosophila
    • Garcia-Alonso, L., S. Romani, and F. Jimenez. 2000. The EGF and FGF receptors mediate neuroglian function to control growth cone decisions during sensory axon guidance in Drosophila. Neuron. 28:741-752.
    • (2000) Neuron , vol.28 , pp. 741-752
    • Garcia-Alonso, L.1    Romani, S.2    Jimenez, F.3
  • 23
    • 0032801630 scopus 로고    scopus 로고
    • Localization of Na,K-ATPase α/β isoforms in rat sciatic nerves: Effect of diabetes and fish oil treatment
    • Gerbi, A., S. Sennoune, S. Pierre, J. Sampol, D. Raccah, P. Vague, and J.M. Maixent. 1999. Localization of Na,K-ATPase α/β isoforms in rat sciatic nerves: effect of diabetes and fish oil treatment. J. Neurochem. 73:719-726.
    • (1999) J. Neurochem. , vol.73 , pp. 719-726
    • Gerbi, A.1    Sennoune, S.2    Pierre, S.3    Sampol, J.4    Raccah, D.5    Vague, P.6    Maixent, J.M.7
  • 24
    • 0035000826 scopus 로고    scopus 로고
    • Neuroligin 3 is a vertebrate gliotactin expressed in the olfactory ensheathing glia, a growth-promoting class of macroglia
    • Gilbert, M., J. Smith, A.J. Roskams, and V.J. Auld. 2001. Neuroligin 3 is a vertebrate gliotactin expressed in the olfactory ensheathing glia, a growth-promoting class of macroglia. Glia. 34:151-164.
    • (2001) Glia , vol.34 , pp. 151-164
    • Gilbert, M.1    Smith, J.2    Roskams, A.J.3    Auld, V.J.4
  • 25
    • 0035576934 scopus 로고    scopus 로고
    • Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier
    • Huber, J.D., R.D. Egleton, and T.P. Davis. 2001. Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci. 24:719-725.
    • (2001) Trends Neurosci. , vol.24 , pp. 719-725
    • Huber, J.D.1    Egleton, R.D.2    Davis, T.P.3
  • 26
    • 0031740862 scopus 로고    scopus 로고
    • Drosophila coracle, a member of the protein 4.1 superfamily, has essential structural functions in the septate junctions and developmental functions in embryonic and adult epithelial cells
    • Lamb, R.S., R.E. Ward, L. Schweizer, and R.G. Fehon. 1998. Drosophila coracle, a member of the protein 4.1 superfamily, has essential structural functions in the septate junctions and developmental functions in embryonic and adult epithelial cells. Mol. Biol. Cell. 9:3505-3519.
    • (1998) Mol. Biol. Cell , vol.9 , pp. 3505-3519
    • Lamb, R.S.1    Ward, R.E.2    Schweizer, L.3    Fehon, R.G.4
  • 27
    • 0029558480 scopus 로고
    • Segmental patterning of heart precursors in Drosophila
    • Lawrence, P.A., R. Bodmer, and J.P. Vincent. 1995. Segmental patterning of heart precursors in Drosophila. Development. 121:4303-4308.
    • (1995) Development , vol.121 , pp. 4303-4308
    • Lawrence, P.A.1    Bodmer, R.2    Vincent, J.P.3
  • 28
    • 0024465457 scopus 로고
    • Molecular characterization and expression of the (Na+/K+)-ATPase α-subunit in Drosophila melanogaster
    • Lebovitz, R.M., K. Takeyasu, and D.M. Fambrough. 1989. Molecular characterization and expression of the (Na+/K+)-ATPase α-subunit in Drosophila melanogaster. EMBO J. 8:193-202.
    • (1989) EMBO J. , vol.8 , pp. 193-202
    • Lebovitz, R.M.1    Takeyasu, K.2    Fambrough, D.M.3
  • 29
    • 0035550517 scopus 로고    scopus 로고
    • Interaction of Na,K-ATPase catalytic subunit with cellular proteins and other endogenous regulators
    • Lopina, O.D. 2001. Interaction of Na, K-ATPase catalytic subunit with cellular proteins and other endogenous regulators. Biochemistry. 66:1122-1131.
    • (2001) Biochemistry , vol.66 , pp. 1122-1131
    • Lopina, O.D.1
  • 30
    • 0028237630 scopus 로고
    • In vitro binding studies suggest a membrane-associated complex between erythroid p55, protein 4.1, and glycophorin C
    • Marfatia, S.M., R.A. Lue, D. Branton, and A.H. Chishti. 1994. In vitro binding studies suggest a membrane-associated complex between erythroid p55, protein 4.1, and glycophorin C.J. Biol. Chem. 269:8631-8634.
    • (1994) J. Biol. Chem. , vol.269 , pp. 8631-8634
    • Marfatia, S.M.1    Lue, R.A.2    Branton, D.3    Chishti, A.H.4
  • 31
    • 0028917977 scopus 로고
    • Identification of the protein 4.1 binding interface on glycophorin C and p55, a homologue of the Drosophila discs-large tumor suppressor protein
    • Marfatia, S.M., R.A. Leu, D. Branton, and A.H. Chishti. 1995. Identification of the protein 4.1 binding interface on glycophorin C and p55, a homologue of the Drosophila discs-large tumor suppressor protein. J. Biol. Chem. 270:715-719.
    • (1995) J. Biol. Chem. , vol.270 , pp. 715-719
    • Marfatia, S.M.1    Leu, R.A.2    Branton, D.3    Chishti, A.H.4
  • 33
    • 0035910097 scopus 로고    scopus 로고
    • A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila
    • Morin, X., R. Daneman, M. Zavortink, and W. Chia. 2001. A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila. Proc. Natl. Acad. Sci. USA. 98:15050-15055.
    • (2001) Proc. Natl. Acad. Sci. USA , vol.98 , pp. 15050-15055
    • Morin, X.1    Daneman, R.2    Zavortink, M.3    Chia, W.4
  • 34
    • 0023262074 scopus 로고
    • Ankyrin binding to (Na+/K+)ATPase and implications for the organization of membrane domains in polarized cells
    • Nelson, W.J., and P.J. Veshnock. 1987. Ankyrin binding to (Na+/K+)ATPase and implications for the organization of membrane domains in polarized cells. Nature. 328:533-536.
    • (1987) Nature , vol.328 , pp. 533-536
    • Nelson, W.J.1    Veshnock, P.J.2
  • 35
    • 0028033098 scopus 로고
    • A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion
    • Oda, H., T. Uemura, Y. Harada, Y. Iwai, and M. Takeichi. 1994. A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion. Dev. Biol. 165:716-726.
    • (1994) Dev. Biol. , vol.165 , pp. 716-726
    • Oda, H.1    Uemura, T.2    Harada, Y.3    Iwai, Y.4    Takeichi, M.5
  • 36
    • 0025296292 scopus 로고
    • The adhesion molecule on glia (AMOG) is widely expressed by astrocytes in developing and adult mouse brain
    • Pagliusi, S.R., M. Schachner, P.H. Seeburg, and B.D. Shivers. 1990. The adhesion molecule on glia (AMOG) is widely expressed by astrocytes in developing and adult mouse brain. Eur. J. Neurosci. 2:471-480.
    • (1990) Eur. J. Neurosci. , vol.2 , pp. 471-480
    • Pagliusi, S.R.1    Schachner, M.2    Seeburg, P.H.3    Shivers, B.D.4
  • 37
    • 0023666143 scopus 로고
    • Characterization and cloning of fascidin III: A glycoprotein expressed on a subset of neurons and axon pathways in Drosophila
    • Patel, N.H., P.M. Snow, and C.S. Goodman. 1987. Characterization and cloning of fascidin III: a glycoprotein expressed on a subset of neurons and axon pathways in Drosophila. Cell. 48:975-988.
    • (1987) Cell , vol.48 , pp. 975-988
    • Patel, N.H.1    Snow, P.M.2    Goodman, C.S.3
  • 38
    • 0030273675 scopus 로고    scopus 로고
    • Presynaptic development at the Drosophila neuromuscular junction: Assembly and localization of presynaptic active zones
    • Prokop, A., M. Landgraf, E. Rushton, K. Broadie, and M. Bate. 1996. Presynaptic development at the Drosophila neuromuscular junction: assembly and localization of presynaptic active zones. Neuron. 17:617-626.
    • (1996) Neuron , vol.17 , pp. 617-626
    • Prokop, A.1    Landgraf, M.2    Rushton, E.3    Broadie, K.4    Bate, M.5
  • 41
    • 0030957351 scopus 로고    scopus 로고
    • Clustering sodium channels at the node of Ranvier: Close encounters of the axon-glia kind
    • Salzer, J.L. 1997. Clustering sodium channels at the node of Ranvier: close encounters of the axon-glia kind. Neuron. 18:843-846.
    • (1997) Neuron , vol.18 , pp. 843-846
    • Salzer, J.L.1
  • 42
    • 0032883802 scopus 로고    scopus 로고
    • The Berkeley Drosophila Genome Project gene disruption project: Single P-element insertions mutating 25% of vital Drosophila genes
    • Spradling, A.C., D. Stern, A. Beaton, E.J. Rhem, T. Laverty, N. Mozden, S. Misra, and G.M. Rubin. 1999. The Berkeley Drosophila Genome Project gene disruption project: single P-element insertions mutating 25% of vital Drosophila genes. Genetics. 153:135-177.
    • (1999) Genetics , vol.153 , pp. 135-177
    • Spradling, A.C.1    Stern, D.2    Beaton, A.3    Rhem, E.J.4    Laverty, T.5    Mozden, N.6    Misra, S.7    Rubin, G.M.8
  • 43
    • 0029014385 scopus 로고
    • Characterization of nervana, a Drosophila melanogaster neuron-specific glycoprotein antigen recognized by anti-horse-radish peroxidase antibodies
    • Sun, B., and P.M. Salvaterra. 1995a. Characterization of nervana, a Drosophila melanogaster neuron-specific glycoprotein antigen recognized by anti-horse-radish peroxidase antibodies. J. Neurochem. 65:434-443.
    • (1995) J. Neurochem. , vol.65 , pp. 434-443
    • Sun, B.1    Salvaterra, P.M.2
  • 46
    • 0028176572 scopus 로고
    • The development of cellular junctions in the Drosophila embryo
    • Tepass, U., and V. Hartenstein. 1994. The development of cellular junctions in the Drosophila embryo. Dev. Biol. 161:563-596.
    • (1994) Dev. Biol. , vol.161 , pp. 563-596
    • Tepass, U.1    Hartenstein, V.2
  • 47
    • 0035674837 scopus 로고    scopus 로고
    • Epithelial cell polarity and cell junctions in Drosophila
    • Tepass, U., G. Tanentzapf, R. Ward, and R. Fehon. 2001. Epithelial cell polarity and cell junctions in Drosophila. Annu. Rev. Genet. 35:747-784.
    • (2001) Annu. Rev. Genet. , vol.35 , pp. 747-784
    • Tepass, U.1    Tanentzapf, G.2    Ward, R.3    Fehon, R.4
  • 49
    • 0032559823 scopus 로고    scopus 로고
    • A conserved functional domain of Drosophila coracle is required for localization at the septate junction and has membrane-organizing activity
    • Ward, R.E., R.S. Lamb, and R.G. Fehon. 1998. A conserved functional domain of Drosophila coracle is required for localization at the septate junction and has membrane-organizing activity. J. Cell Biol. 140:1463-1473.
    • (1998) J. Cell Biol. , vol.140 , pp. 1463-1473
    • Ward, R.E.1    Lamb, R.S.2    Fehon, R.G.3
  • 50
    • 0034809326 scopus 로고    scopus 로고
    • The protein 4.1, ezrin, radixin, moesin (FERM) domain of Drosophila Coracle, a cytoplasmic component of the septate junction, provides functions essential for embryonic development and imaginal cell proliferation
    • Ward, R.E., L. Schweizer, R.S. Lamb, and R.G. Fehon. 2001. The protein 4.1, ezrin, radixin, moesin (FERM) domain of Drosophila Coracle, a cytoplasmic component of the septate junction, provides functions essential for embryonic development and imaginal cell proliferation. Genetics. 159:219-228.
    • (2001) Genetics , vol.159 , pp. 219-228
    • Ward, R.E.1    Schweizer, L.2    Lamb, R.S.3    Fehon, R.G.4
  • 51
    • 0029819449 scopus 로고    scopus 로고
    • Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia
    • Woods, D.F., C. Hough, D. Peel, G. Callaini, and P.J. Bryant. 1996. Dlg protein is required for junction structure, cell polarity, and proliferation control in Drosophila epithelia. J. Cell Biol. 134:1469-1482.
    • (1996) J. Cell Biol. , vol.134 , pp. 1469-1482
    • Woods, D.F.1    Hough, C.2    Peel, D.3    Callaini, G.4    Bryant, P.J.5
  • 52
    • 0032787227 scopus 로고    scopus 로고
    • Organization and transcriptional regulation of Drosophila Na(+), K(+)- ATPase β subunit genes: Nrv1 and Nrv2
    • Xu, P., B. Sun, and P.M. Salvaterra. 1999. Organization and transcriptional regulation of Drosophila Na(+), K(+)- ATPase β subunit genes: Nrv1 and Nrv2. Gene. 236:303-313.
    • (1999) Gene , vol.236 , pp. 303-313
    • Xu, P.1    Sun, B.2    Salvaterra, P.M.3


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