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J Cell Biol. 1996 May 1; 133(3): 647–655.
PMCID: PMC2120821

Neuroglian-mediated cell adhesion induces assembly of the membrane skeleton at cell contact sites


The protein ankyrin links integral membrane proteins to the spectrin- based membrane skeleton. Ankyrin is often concentrated within restricted membrane domains of polarized epithelia and neurons, but the mechanisms responsible for membrane targeting and its segregation within a continuous lipid bilayer remain unexplained. We provide evidence that neuroglian, a cell adhesion molecule related to L1 and neurofascin, can transmit positional information directly to ankyrin and thereby polarize its distribution in Drosophila S2 tissue culture cells. Ankyrin was not normally associated with the plasma membrane of these cells. Upon expression of an inducible neuroglian minigene, however, cells aggregated into large clusters and ankyrin became concentrated at sites of cell-cell contact. Spectrin was also recruited to sites of cell contact in response to neuroglian expression. The accumulation of ankyrin at cell contacts required the presence of the cytoplasmic domain of neuroglian since a glycosyl phosphatidylinositol- linked form of neuroglian failed to recruit ankyrin to sites of cell- cell contact. Double-labeling experiments revealed that, whereas ankyrin was strictly associated with sites of cell-cell contact, neuroglian was more broadly distributed over the cell surface. A direct interaction between neuroglian and ankyrin was demonstrated using yeast two-hybrid analysis. Thus, neuroglian appears to be activated by extracellular adhesion so that ankyrin and the membrane skeleton selectively associate with sites of cell contact and not with other regions of the plasma membrane.

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Selected References

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  • Bennett V. Spectrin-based membrane skeleton: a multipotential adaptor between plasma membrane and cytoplasm. Physiol Rev. 1990 Oct;70(4):1029–1065. [PubMed]
  • Bennett V, Gilligan DM. The spectrin-based membrane skeleton and micron-scale organization of the plasma membrane. Annu Rev Cell Biol. 1993;9:27–66. [PubMed]
  • Bieber AJ, Snow PM, Hortsch M, Patel NH, Jacobs JR, Traquina ZR, Schilling J, Goodman CS. Drosophila neuroglian: a member of the immunoglobulin superfamily with extensive homology to the vertebrate neural adhesion molecule L1. Cell. 1989 Nov 3;59(3):447–460. [PubMed]
  • Byers TJ, Husain-Chishti A, Dubreuil RR, Branton D, Goldstein LS. Sequence similarity of the amino-terminal domain of Drosophila beta spectrin to alpha actinin and dystrophin. J Cell Biol. 1989 Oct;109(4 Pt 1):1633–1641. [PMC free article] [PubMed]
  • Chen C, Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. [PMC free article] [PubMed]
  • Cox JV, Stack JH, Lazarides E. Erythroid anion transporter assembly is mediated by a developmentally regulated recruitment onto a preassembled membrane cytoskeleton. J Cell Biol. 1987 Sep;105(3):1405–1416. [PMC free article] [PubMed]
  • Davis JQ, Bennett V. Ankyrin binding activity shared by the neurofascin/L1/NrCAM family of nervous system cell adhesion molecules. J Biol Chem. 1994 Nov 4;269(44):27163–27166. [PubMed]
  • Davis JQ, McLaughlin T, Bennett V. Ankyrin-binding proteins related to nervous system cell adhesion molecules: candidates to provide transmembrane and intercellular connections in adult brain. J Cell Biol. 1993 Apr;121(1):121–133. [PMC free article] [PubMed]
  • Deng H, Lee JK, Goldstein LS, Branton D. Drosophila development requires spectrin network formation. J Cell Biol. 1995 Jan;128(1-2):71–79. [PMC free article] [PubMed]
  • Doherty P, Walsh FS. Signal transduction events underlying neurite outgrowth stimulated by cell adhesion molecules. Curr Opin Neurobiol. 1994 Feb;4(1):49–55. [PubMed]
  • Drenckhahn D, Bennett V. Polarized distribution of Mr 210,000 and 190,000 analogs of erythrocyte ankyrin along the plasma membrane of transporting epithelia, neurons and photoreceptors. Eur J Cell Biol. 1987 Jun;43(3):479–486. [PubMed]
  • Dubreuil R, Byers TJ, Branton D, Goldstein LS, Kiehart DP. Drosophilia spectrin. I. Characterization of the purified protein. J Cell Biol. 1987 Nov;105(5):2095–2102. [PMC free article] [PubMed]
  • Dubreuil RR, Yu J. Ankyrin and beta-spectrin accumulate independently of alpha-spectrin in Drosophila. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10285–10289. [PMC free article] [PubMed]
  • Durfee T, Becherer K, Chen PL, Yeh SH, Yang Y, Kilburn AE, Lee WH, Elledge SJ. The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 1993 Apr;7(4):555–569. [PubMed]
  • Evan GI, Lewis GK, Ramsay G, Bishop JM. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985 Dec;5(12):3610–3616. [PMC free article] [PubMed]
  • Ginsberg MH, Du X, Plow EF. Inside-out integrin signalling. Curr Opin Cell Biol. 1992 Oct;4(5):766–771. [PubMed]
  • Gregorio CC, Repasky EA, Fowler VM, Black JD. Dynamic properties of ankyrin in T lymphocytes: colocalization with spectrin and protein kinase C beta. J Cell Biol. 1994 Apr;125(2):345–358. [PMC free article] [PubMed]
  • Hammerton RW, Krzeminski KA, Mays RW, Ryan TA, Wollner DA, Nelson WJ. Mechanism for regulating cell surface distribution of Na+,K(+)-ATPase in polarized epithelial cells. Science. 1991 Nov 8;254(5033):847–850. [PubMed]
  • Hortsch M, Bieber AJ, Patel NH, Goodman CS. Differential splicing generates a nervous system-specific form of Drosophila neuroglian. Neuron. 1990 May;4(5):697–709. [PubMed]
  • Hortsch M, Wang YM, Marikar Y, Bieber AJ. The cytoplasmic domain of the Drosophila cell adhesion molecule neuroglian is not essential for its homophilic adhesive properties in S2 cells. J Biol Chem. 1995 Aug 11;270(32):18809–18817. [PubMed]
  • Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 1993 Sep;9(9):317–321. [PubMed]
  • Kordeli E, Lambert S, Bennett V. AnkyrinG. A new ankyrin gene with neural-specific isoforms localized at the axonal initial segment and node of Ranvier. J Biol Chem. 1995 Feb 3;270(5):2352–2359. [PubMed]
  • Lee HS, Simon JA, Lis JT. Structure and expression of ubiquitin genes of Drosophila melanogaster. Mol Cell Biol. 1988 Nov;8(11):4727–4735. [PMC free article] [PubMed]
  • Lee JK, Coyne RS, Dubreuil RR, Goldstein LS, Branton D. Cell shape and interaction defects in alpha-spectrin mutants of Drosophila melanogaster. J Cell Biol. 1993 Dec;123(6 Pt 2):1797–1809. [PMC free article] [PubMed]
  • Lombardo CR, Weed SA, Kennedy SP, Forget BG, Morrow JS. Beta II-spectrin (fodrin) and beta I epsilon 2-spectrin (muscle) contain NH2- and COOH-terminal membrane association domains (MAD1 and MAD2). J Biol Chem. 1994 Nov 18;269(46):29212–29219. [PubMed]
  • Marrs JA, Andersson-Fisone C, Jeong MC, Cohen-Gould L, Zurzolo C, Nabi IR, Rodriguez-Boulan E, Nelson WJ. Plasticity in epithelial cell phenotype: modulation by expression of different cadherin cell adhesion molecules. J Cell Biol. 1995 Apr;129(2):507–519. [PMC free article] [PubMed]
  • Matter K, Mellman I. Mechanisms of cell polarity: sorting and transport in epithelial cells. Curr Opin Cell Biol. 1994 Aug;6(4):545–554. [PubMed]
  • McNeill H, Ozawa M, Kemler R, Nelson WJ. Novel function of the cell adhesion molecule uvomorulin as an inducer of cell surface polarity. Cell. 1990 Jul 27;62(2):309–316. [PubMed]
  • Miyamoto S, Akiyama SK, Yamada KM. Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function. Science. 1995 Feb 10;267(5199):883–885. [PubMed]
  • Moon RT, Lazarides E. Biogenesis of the avian erythroid membrane skeleton: receptor-mediated assembly and stabilization of ankyrin (goblin) and spectrin. J Cell Biol. 1984 May;98(5):1899–1904. [PMC free article] [PubMed]
  • Morrow JS, Cianci CD, Ardito T, Mann AS, Kashgarian M. Ankyrin links fodrin to the alpha subunit of Na,K-ATPase in Madin-Darby canine kidney cells and in intact renal tubule cells. J Cell Biol. 1989 Feb;108(2):455–465. [PMC free article] [PubMed]
  • Nelson WJ, Lazarides E. The patterns of expression of two ankyrin isoforms demonstrate distinct steps in the assembly of the membrane skeleton in neuronal morphogenesis. Cell. 1984 Dec;39(2 Pt 1):309–320. [PubMed]
  • Nelson WJ, Veshnock PJ. Modulation of fodrin (membrane skeleton) stability by cell-cell contact in Madin-Darby canine kidney epithelial cells. J Cell Biol. 1987 Jun;104(6):1527–1537. [PMC free article] [PubMed]
  • Nelson WJ, Shore EM, Wang AZ, Hammerton RW. Identification of a membrane-cytoskeletal complex containing the cell adhesion molecule uvomorulin (E-cadherin), ankyrin, and fodrin in Madin-Darby canine kidney epithelial cells. J Cell Biol. 1990 Feb;110(2):349–357. [PMC free article] [PubMed]
  • Nelson WJ. Regulation of cell surface polarity from bacteria to mammals. Science. 1992 Nov 6;258(5084):948–955. [PubMed]
  • Peters LL, John KM, Lu FM, Eicher EM, Higgins A, Yialamas M, Turtzo LC, Otsuka AJ, Lux SE. Ank3 (epithelial ankyrin), a widely distributed new member of the ankyrin gene family and the major ankyrin in kidney, is expressed in alternatively spliced forms, including forms that lack the repeat domain. J Cell Biol. 1995 Jul;130(2):313–330. [PMC free article] [PubMed]
  • Podack ER, Kupfer A. T-cell effector functions: mechanisms for delivery of cytotoxicity and help. Annu Rev Cell Biol. 1991;7:479–504. [PubMed]
  • Schneider I. Cell lines derived from late embryonic stages of Drosophila melanogaster. J Embryol Exp Morphol. 1972 Apr;27(2):353–365. [PubMed]
  • Simons K, Dupree P, Fiedler K, Huber LA, Kobayashi T, Kurzchalia T, Olkkonen V, Pimplikar S, Parton R, Dotti C. Biogenesis of cell-surface polarity in epithelial cells and neurons. Cold Spring Harb Symp Quant Biol. 1992;57:611–619. [PubMed]
  • Steiner JP, Bennett V. Ankyrin-independent membrane protein-binding sites for brain and erythrocyte spectrin. J Biol Chem. 1988 Oct 5;263(28):14417–14425. [PubMed]

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