PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
 
J Cell Biol. 1995 September 2; 130(6): 1447–1459.
PMCID: PMC2120579

Intracellular routing of wild-type and mutated polymeric immunoglobulin receptor in hippocampal neurons in culture

Abstract

Certain epithelial cells synthesize the polymeric immunoglobulin receptor (pIgR) to transport immunoglobulins (Igs) A and M into external secretions. In polarized epithelia, newly synthesized receptor is first delivered to the basolateral plasma membrane and is then, after binding the Ig, transcytosed to the apical plasma membrane, where the receptor-ligand complex is released by proteolytic cleavage. In a previous work (Ikonen et al., 1993), we implied the existence of a dendro-axonal transcytotic pathway for the rabbit pIgR expressed in hippocampal neurons via the Semliki Forest Virus (SFV) expression system. By labeling surface-exposed pIgR in live neuronal cells, we now show (a) internalization of the receptor from the dendritic plasma membrane to the dendritic early endosomes, (b) redistribution of the receptor from the dendritic to the axonal domain, (c) inhibition of this movement by brefeldin A (BFA) and (d) stimulation by the activation of protein kinase C (PKC) via phorbol myristate acetate (PMA). In addition, we show that a mutant form of the receptor lacking the epithelial basolateral sorting signal is directly delivered to the axonal domain of hippocampal neurons. Although this mutant is internalized into early endosomes, no transcytosis to the dendrites could be observed. In epithelial Madin-Darby Canine Kidney (MDCK) cells, the mutant receptor could also be internalized into basolaterally derived early endosomes. These results suggest the existence of a dendro-axonal transcytotic pathway in neuronal cells which shares similarities with the basolateral to apical transcytosis in epithelial cells and constitute the basis for the future analysis of its physiological role.

Full Text

The Full Text of this article is available as a PDF (6.5M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Apodaca G, Katz LA, Mostov KE. Receptor-mediated transcytosis of IgA in MDCK cells is via apical recycling endosomes. J Cell Biol. 1994 Apr;125(1):67–86. [PMC free article] [PubMed]
  • Apodaca G, Bomsel M, Arden J, Breitfeld PP, Tang K, Mostov KE. The polymeric immunoglobulin receptor. A model protein to study transcytosis. J Clin Invest. 1991 Jun;87(6):1877–1882. [PMC free article] [PubMed]
  • Aroeti B, Casanova J, Okamoto C, Cardone M, Pollack A, Tang K, Mostov K. Polymeric immunoglobulin receptor. Int Rev Cytol. 1992;137B:157–168. [PubMed]
  • Barroso M, Sztul ES. Basolateral to apical transcytosis in polarized cells is indirect and involves BFA and trimeric G protein sensitive passage through the apical endosome. J Cell Biol. 1994 Jan;124(1-2):83–100. [PMC free article] [PubMed]
  • Bartles JR, Feracci HM, Stieger B, Hubbard AL. Biogenesis of the rat hepatocyte plasma membrane in vivo: comparison of the pathways taken by apical and basolateral proteins using subcellular fractionation. J Cell Biol. 1987 Sep;105(3):1241–1251. [PMC free article] [PubMed]
  • Bomsel M, Mostov K. Role of heterotrimeric G proteins in membrane traffic. Mol Biol Cell. 1992 Dec;3(12):1317–1328. [PMC free article] [PubMed]
  • Bottenstein JE, Sato GH. Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci U S A. 1979 Jan;76(1):514–517. [PubMed]
  • Brändli AW, Adamson ED, Simons K. Transcytosis of epidermal growth factor. The epidermal growth factor receptor mediates uptake but not transcytosis. J Biol Chem. 1991 May 5;266(13):8560–8566. [PubMed]
  • Breitfeld PP, Harris JM, Mostov KE. Postendocytotic sorting of the ligand for the polymeric immunoglobulin receptor in Madin-Darby canine kidney cells. J Cell Biol. 1989 Aug;109(2):475–486. [PMC free article] [PubMed]
  • Brown DA, Crise B, Rose JK. Mechanism of membrane anchoring affects polarized expression of two proteins in MDCK cells. Science. 1989 Sep 29;245(4925):1499–1501. [PubMed]
  • Caceres A, Banker G, Steward O, Binder L, Payne M. MAP2 is localized to the dendrites of hippocampal neurons which develop in culture. Brain Res. 1984 Apr;315(2):314–318. [PubMed]
  • Cardone MH, Smith BL, Song W, Mochly-Rosen D, Mostov KE. Phorbol myristate acetate-mediated stimulation of transcytosis and apical recycling in MDCK cells. J Cell Biol. 1994 Mar;124(5):717–727. [PMC free article] [PubMed]
  • Casanova JE, Breitfeld PP, Ross SA, Mostov KE. Phosphorylation of the polymeric immunoglobulin receptor required for its efficient transcytosis. Science. 1990 May 11;248(4956):742–745. [PubMed]
  • Casanova JE, Apodaca G, Mostov KE. An autonomous signal for basolateral sorting in the cytoplasmic domain of the polymeric immunoglobulin receptor. Cell. 1991 Jul 12;66(1):65–75. [PubMed]
  • Cid-Arregui A, Parton RG, Simons K, Dotti CG. Nocodazole-dependent transport, and brefeldin A--sensitive processing and sorting, of newly synthesized membrane proteins in cultured neurons. J Neurosci. 1995 Jun;15(6):4259–4269. [PubMed]
  • Craig AM, Banker G. Neuronal polarity. Annu Rev Neurosci. 1994;17:267–310. [PubMed]
  • Craig AM, Blackstone CD, Huganir RL, Banker G. The distribution of glutamate receptors in cultured rat hippocampal neurons: postsynaptic clustering of AMPA-selective subunits. Neuron. 1993 Jun;10(6):1055–1068. [PubMed]
  • Dotti CG, Banker GA. Experimentally induced alteration in the polarity of developing neurons. Nature. 1987 Nov 19;330(6145):254–256. [PubMed]
  • Dotti CG, Simons K. Polarized sorting of viral glycoproteins to the axon and dendrites of hippocampal neurons in culture. Cell. 1990 Jul 13;62(1):63–72. [PubMed]
  • Dotti CG, Banker G. Intracellular organization of hippocampal neurons during the development of neuronal polarity. J Cell Sci Suppl. 1991;15:75–84. [PubMed]
  • Dotti CG, Sullivan CA, Banker GA. The establishment of polarity by hippocampal neurons in culture. J Neurosci. 1988 Apr;8(4):1454–1468. [PubMed]
  • Evinger C, Erichsen JT. Transsynaptic retrograde transport of fragment C of tetanus toxin demonstrated by immunohistochemical localization. Brain Res. 1986 Aug 20;380(2):383–388. [PubMed]
  • Fabian RH. Retrograde axonal transport and transcytosis of immunoglobulins: implications for the pathogenesis of autoimmune motor neuron disease. Adv Neurol. 1991;56:433–444. [PubMed]
  • Fletcher TL, Cameron P, De Camilli P, Banker G. The distribution of synapsin I and synaptophysin in hippocampal neurons developing in culture. J Neurosci. 1991 Jun;11(6):1617–1626. [PubMed]
  • Freier S, Eran M, Faber J. Effect of cholecystokinin and of its antagonist, of atropine, and of food on the release of immunoglobulin A and immunoglobulin G specific antibodies in the rat intestine. Gastroenterology. 1987 Dec;93(6):1242–1246. [PubMed]
  • Friden PM, Walus LR, Musso GF, Taylor MA, Malfroy B, Starzyk RM. Anti-transferrin receptor antibody and antibody-drug conjugates cross the blood-brain barrier. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4771–4775. [PubMed]
  • Ghitescu L, Bendayan M. Transendothelial transport of serum albumin: a quantitative immunocytochemical study. J Cell Biol. 1992 May;117(4):745–755. [PMC free article] [PubMed]
  • Gonnella PA, Siminoski K, Murphy RA, Neutra MR. Transepithelial transport of epidermal growth factor by absorptive cells of suckling rat ileum. J Clin Invest. 1987 Jul;80(1):22–32. [PMC free article] [PubMed]
  • Goslin K, Banker G. Experimental observations on the development of polarity by hippocampal neurons in culture. J Cell Biol. 1989 Apr;108(4):1507–1516. [PMC free article] [PubMed]
  • Hashida R, Anamizu C, Kimura J, Ohkuma S, Yoshida Y, Takano T. Transcellular transport of lipoprotein through arterial endothelial cells in monolayer culture. Cell Struct Funct. 1986 Mar;11(1):31–42. [PubMed]
  • Hirt RP, Hughes GJ, Frutiger S, Michetti P, Perregaux C, Poulain-Godefroy O, Jeanguenat N, Neutra MR, Kraehenbuhl JP. Transcytosis of the polymeric Ig receptor requires phosphorylation of serine 664 in the absence but not the presence of dimeric IgA. Cell. 1993 Jul 30;74(2):245–255. [PubMed]
  • de Hoop MJ, Dotti CG. Membrane traffic in polarized neurons in culture. J Cell Sci Suppl. 1993;17:85–92. [PubMed]
  • de Hoop MJ, Huber LA, Stenmark H, Williamson E, Zerial M, Parton RG, Dotti CG. The involvement of the small GTP-binding protein Rab5a in neuronal endocytosis. Neuron. 1994 Jul;13(1):11–22. [PubMed]
  • Huber LA, Pimplikar S, Parton RG, Virta H, Zerial M, Simons K. Rab8, a small GTPase involved in vesicular traffic between the TGN and the basolateral plasma membrane. J Cell Biol. 1993 Oct;123(1):35–45. [PMC free article] [PubMed]
  • Huber LA, de Hoop MJ, Dupree P, Zerial M, Simons K, Dotti C. Protein transport to the dendritic plasma membrane of cultured neurons is regulated by rab8p. J Cell Biol. 1993 Oct;123(1):47–55. [PMC free article] [PubMed]
  • Hunziker W, Mellman I. Expression of macrophage-lymphocyte Fc receptors in Madin-Darby canine kidney cells: polarity and transcytosis differ for isoforms with or without coated pit localization domains. J Cell Biol. 1989 Dec;109(6 Pt 2):3291–3302. [PMC free article] [PubMed]
  • Hunziker W, Mâle P, Mellman I. Differential microtubule requirements for transcytosis in MDCK cells. EMBO J. 1990 Nov;9(11):3515–3525. [PubMed]
  • Hunziker W, Whitney JA, Mellman I. Brefeldin A and the endocytic pathway. Possible implications for membrane traffic and sorting. FEBS Lett. 1992 Jul 27;307(1):93–96. [PubMed]
  • Killisch I, Dotti CG, Laurie DJ, Lüddens H, Seeburg PH. Expression patterns of GABAA receptor subtypes in developing hippocampal neurons. Neuron. 1991 Dec;7(6):927–936. [PubMed]
  • King GL, Johnson SM. Receptor-mediated transport of insulin across endothelial cells. Science. 1985 Mar 29;227(4694):1583–1586. [PubMed]
  • Kraehenbuhl JP, Neutra MR. Transepithelial transport and mucosal defence II: secretion of IgA. Trends Cell Biol. 1992 Jun;2(6):170–174. [PubMed]
  • Kühn LC, Kraehenbuhl JP. Monoclonal antibodies recognizing the secreted and membrane domains of the IgA dimer receptor. Ann N Y Acad Sci. 1983 Jun 30;409:751–759. [PubMed]
  • LaRocca CD, Wiley RG. Monoclonal anti-Thy 1 antibody (OX7) is axonally transported in rat nervous system. Brain Res. 1988 May 24;449(1-2):381–385. [PubMed]
  • Liljeström P, Garoff H. A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology (N Y) 1991 Dec;9(12):1356–1361. [PubMed]
  • Van Lookeren Campagne M, Dotti CG, Jap Tjoen San ER, Verkleij AJ, Gispen WH, Oestreicher AB. B-50/GAP43 localization in polarized hippocampal neurons in vitro: an ultrastructural quantitative study. Neuroscience. 1992 Sep;50(1):35–52. [PubMed]
  • Mostov K. Protein traffic in polarized epithelial cells: the polymeric immunoglobulin receptor as a model system. J Cell Sci Suppl. 1993;17:21–26. [PubMed]
  • Mostov KE, Deitcher DL. Polymeric immunoglobulin receptor expressed in MDCK cells transcytoses IgA. Cell. 1986 Aug 15;46(4):613–621. [PubMed]
  • Mostov K, Apodaca G, Aroeti B, Okamoto C. Plasma membrane protein sorting in polarized epithelial cells. J Cell Biol. 1992 Feb;116(3):577–583. [PMC free article] [PubMed]
  • Nelson WJ. Regulation of cell surface polarity from bacteria to mammals. Science. 1992 Nov 6;258(5084):948–955. [PubMed]
  • Okamoto CT, Shia SP, Bird C, Mostov KE, Roth MG. The cytoplasmic domain of the polymeric immunoglobulin receptor contains two internalization signals that are distinct from its basolateral sorting signal. J Biol Chem. 1992 May 15;267(14):9925–9932. [PubMed]
  • Okamoto CT, Song W, Bomsel M, Mostov KE. Rapid internalization of the polymeric immunoglobulin receptor requires phosphorylated serine 726. J Biol Chem. 1994 Jun 3;269(22):15676–15682. [PubMed]
  • Pickard GE, Silverman AJ. Direct retinal projections to the hypothalamus, piriform cortex, and accessory optic nuclei in the golden hamster as demonstrated by a sensitive anterograde horseradish peroxidase technique. J Comp Neurol. 1981 Feb 10;196(1):155–172. [PubMed]
  • Raphael GD, Druce HM, Baraniuk JN, Kaliner MA. Pathophysiology of rhinitis. 1. Assessment of the sources of protein in methacholine-induced nasal secretions. Am Rev Respir Dis. 1988 Aug;138(2):413–420. [PubMed]
  • Rodman JS, Mercer RW, Stahl PD. Endocytosis and transcytosis. Curr Opin Cell Biol. 1990 Aug;2(4):664–672. [PubMed]
  • Rodriguez-Boulan E, Powell SK. Polarity of epithelial and neuronal cells. Annu Rev Cell Biol. 1992;8:395–427. [PubMed]
  • Ruda M, Coulter JD. Axonal and transneuronal transport of wheat germ agglutinin demonstrated by immunocytochemistry. Brain Res. 1982 Oct 14;249(2):237–246. [PubMed]
  • Schwab ME, Thoenen H. Selective binding, uptake, and retrograde transport of tetanus toxin by nerve terminals in the rat iris. An electron microscope study using colloidal gold as a tracer. J Cell Biol. 1978 Apr;77(1):1–13. [PMC free article] [PubMed]
  • Schwab ME, Suda K, Thoenen H. Selective retrograde transsynaptic transfer of a protein, tetanus toxin, subsequent to its retrograde axonal transport. J Cell Biol. 1979 Sep;82(3):798–810. [PMC free article] [PubMed]
  • Siminoski K, Gonnella P, Bernanke J, Owen L, Neutra M, Murphy RA. Uptake and transepithelial transport of nerve growth factor in suckling rat ileum. J Cell Biol. 1986 Nov;103(5):1979–1990. [PMC free article] [PubMed]
  • Simons M, Ikonen E, Tienari PJ, Cid-Arregui A, Mönning U, Beyreuther K, Dotti CG. Intracellular routing of human amyloid protein precursor: axonal delivery followed by transport to the dendrites. J Neurosci Res. 1995 May 1;41(1):121–128. [PubMed]
  • Soda R, Tavassoli M. Transendothelial transport (transcytosis) of iron-transferrin complex in the bone marrow. J Ultrastruct Res. 1984 Jul;88(1):18–29. [PubMed]
  • Solari R, Kühn L, Kraehenbuhl JP. Antibodies recognizing different domains of the polymeric immunoglobulin receptor. J Biol Chem. 1985 Jan 25;260(2):1141–1145. [PubMed]
  • Sooranna SR, Contractor SF. Vectorial transcytosis of immunoglobulin G by human term trophoblast cells in culture. Exp Cell Res. 1991 Jan;192(1):41–45. [PubMed]
  • Song W, Bomsel M, Casanova J, Vaerman JP, Mostov K. Stimulation of transcytosis of the polymeric immunoglobulin receptor by dimeric IgA. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):163–166. [PubMed]
  • Sztul E. Transcytotic vesicle fusion with plasma membrane. Methods Enzymol. 1992;219:44–51. [PubMed]
  • Wandinger-Ness A, Bennett MK, Antony C, Simons K. Distinct transport vesicles mediate the delivery of plasma membrane proteins to the apical and basolateral domains of MDCK cells. J Cell Biol. 1990 Sep;111(3):987–1000. [PMC free article] [PubMed]
  • Wilson ID, Soltis RD, Olson RE, Erlandsen SL. Cholinergic stimulation of immunoglobulin A secretion in rat intestine. Gastroenterology. 1982 Oct;83(4):881–888. [PubMed]
  • Wollner DA, Krzeminski KA, Nelson WJ. Remodeling the cell surface distribution of membrane proteins during the development of epithelial cell polarity. J Cell Biol. 1992 Feb;116(4):889–899. [PMC free article] [PubMed]
  • Zurzolo C, Le Bivic A, Quaroni A, Nitsch L, Rodriguez-Boulan E. Modulation of transcytotic and direct targeting pathways in a polarized thyroid cell line. EMBO J. 1992 Jun;11(6):2337–2344. [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press