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PMID: 21811244 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Local BMP receptor activation at adherens junctions in the Drosophila germline stem cell niche.

Nature communications ·Vol. 2 ·2011-08-02 ·Pages 415

Michel M, Raabe I, Kupinski AP, Pérez-Palencia R, Bökel C

Abstract

According to the stem cell niche synapse hypothesis postulated for the mammalian haematopoietic system, spatial specificity of niche signals is maximized by subcellularly restricting signalling to cadherin-based adherens junctions between individual niche and stem cells. However, such a synapse has never been observed directly, in part, because tools to detect active growth factor receptors with subcellular resolution were not available. Here we describe a novel fluorescence-based reporter that directly visualizes bone morphogenetic protein (BMP) receptor activation and show that in the Drosophila testis a BMP niche signal is transmitted preferentially at adherens junctions between hub and germline stem cells, resembling the proposed synapse organization. Ligand secretion involves the exocyst complex and the Rap activator Gef26, both of which are also required for Cadherin trafficking towards adherens junctions. We, therefore, propose that local generation of the BMP signal is achieved through shared use of the Cadherin transport machinery.

MeSH Terms
Adherens Junctions/genetics,metabolism Animals Bone Morphogenetic Proteins/metabolism Drosophila/genetics,metabolism Drosophila Proteins/genetics,metabolism Germ Cells/cytology,metabolism Male Protein Serine-Threonine Kinases/genetics,metabolism Receptors, Cell Surface/genetics,metabolism Signal Transduction Stem Cell Niche Stem Cells/cytology,metabolism Testis/cytology,metabolism
Chemicals
Bone Morphogenetic Proteins Drosophila Proteins Receptors, Cell Surface tkv protein, Drosophila Protein Serine-Threonine Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Michel Marcus
Center for Regenerative Therapies Dresden (CRTD), TU Dresden, Tatzberg, Germany.
Raabe Isabel
Kupinski Adam P
Pérez-Palencia Raquel
Bökel Christian
References (57)
57 references, click to expand
  1. The Decapentaplegic morphogen gradient: a precise definition.
    Curr Opin Cell Biol. 2008 Apr;20(2):137-43 PMID: 18329870
  2. The TGF beta receptor activation process: an inhibitor- to substrate-binding switch.
    Mol Cell. 2001 Sep;8(3):671-82 PMID: 11583628
  3. Kinetics of morphogen gradient formation.
    Science. 2007 Jan 26;315(5811):521-5 PMID: 17255514
  4. A discrete transcriptional silencer in the bam gene determines asymmetric division of the Drosophila germline stem cell.
    Development. 2003 Mar;130(6):1159-70 PMID: 12571107
  5. Stem cell self-renewal specified by JAK-STAT activation in response to a support cell cue.
    Science. 2001 Dec 21;294(5551):2542-5 PMID: 11752574
  6. A conserved system for dorsal-ventral patterning in insects and vertebrates involving sog and chordin.
    Nature. 1995 Jul 20;376(6537):249-53 PMID: 7617035
  7. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein.
    Nat Biotechnol. 2004 Dec;22(12):1567-72 PMID: 15558047
  8. Mutations in the exocyst component Sec5 disrupt neuronal membrane traffic, but neurotransmitter release persists.
    Neuron. 2003 Feb 6;37(3):433-47 PMID: 12575951
  9. Regulation of stem cell maintenance and transit amplifying cell proliferation by tgf-beta signaling in Drosophila spermatogenesis.
    Curr Biol. 2003 Dec 2;13(23):2065-72 PMID: 14653996
  10. Gradient formation of the TGF-beta homolog Dpp.
    Cell. 2000 Dec 8;103(6):981-91 PMID: 11136982
  11. Bone-marrow haematopoietic-stem-cell niches.
    Nat Rev Immunol. 2006 Feb;6(2):93-106 PMID: 16491134
  12. Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors.
    Mol Biol Cell. 2000 Mar;11(3):1023-35 PMID: 10712517
  13. A changing morphogen gradient is interpreted by continuous transduction flow.
    Development. 2002 May;129(9):2167-80 PMID: 11959826
  14. A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion.
    Dev Biol. 1994 Oct;165(2):716-26 PMID: 7958432
  15. chinmo is a functional effector of the JAK/STAT pathway that regulates eye development, tumor formation, and stem cell self-renewal in Drosophila.
    Dev Cell. 2010 Apr 20;18(4):556-68 PMID: 20412771
  16. Precision of the Dpp gradient.
    Development. 2008 Mar;135(6):1137-46 PMID: 18296653
  17. Visualizing long-range movement of the morphogen Xnr2 in the Xenopus embryo.
    Curr Biol. 2004 Nov 9;14(21):1916-23 PMID: 15530392
  18. Rap1 GTPase regulation of adherens junction positioning and cell adhesion.
    Science. 2002 Feb 15;295(5558):1285-8 PMID: 11847339
  19. Posterior localization of vasa protein correlates with, but is not sufficient for, pole cell development.
    Genes Dev. 1990 Jun;4(6):905-21 PMID: 2384213
  20. The endocytic pathway and formation of the Wingless morphogen gradient.
    Development. 2006 Jan;133(2):307-17 PMID: 16354714
  21. Synergistic signaling by two BMP ligands through the SAX and TKV receptors controls wing growth and patterning in Drosophila.
    Development. 1998 Oct;125(20):3977-87 PMID: 9735359
  22. Coordinated cell-shape changes control epithelial movement in zebrafish and Drosophila.
    Development. 2006 Jul;133(14):2671-81 PMID: 16794032
  23. A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila.
    Nature. 2007 Jul 12;448(7150):151-6 PMID: 17625558
  24. Ectopic expression of the Drosophila Bam protein eliminates oogenic germline stem cells.
    Development. 1997 Sep;124(18):3651-62 PMID: 9342057
  25. A molecular mechanism directly linking E-cadherin adhesion to initiation of epithelial cell surface polarity.
    J Cell Biol. 2007 Jul 16;178(2):323-35 PMID: 17635938
  26. Circularly permuted green fluorescent proteins engineered to sense Ca2+.
    Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3197-202 PMID: 11248055
  27. A misexpression screen reveals effects of bag-of-marbles and TGF beta class signaling on the Drosophila male germ-line stem cell lineage.
    Genetics. 2004 Jun;167(2):707-23 PMID: 15238523
  28. The exocyst component Sec5 is present on endocytic vesicles in the oocyte of Drosophila melanogaster.
    J Cell Biol. 2005 Jun 20;169(6):953-63 PMID: 15955846
  29. Gbb/Bmp signaling is essential for maintaining germline stem cells and for repressing bam transcription in the Drosophila testis.
    Development. 2004 Mar;131(6):1365-75 PMID: 14973292
  30. Germline stem cells anchored by adherens junctions in the Drosophila ovary niches.
    Science. 2002 Jun 7;296(5574):1855-7 PMID: 12052957
  31. Zfh-1 controls somatic stem cell self-renewal in the Drosophila testis and nonautonomously influences germline stem cell self-renewal.
    Cell Stem Cell. 2008 Jul 3;3(1):44-54 PMID: 18593558
  32. dpp induces mesodermal gene expression in Drosophila.
    Nature. 1994 Dec 22-29;372(6508):783-6 PMID: 7997266
  33. Rab11 mediates post-Golgi trafficking of rhodopsin to the photosensitive apical membrane of Drosophila photoreceptors.
    Development. 2005 Apr;132(7):1487-97 PMID: 15728675
  34. Germline self-renewal requires cyst stem cells and stat regulates niche adhesion in Drosophila testes.
    Nat Cell Biol. 2010 Aug;12(8):806-11 PMID: 20622868
  35. Drosophila exocyst components Sec5, Sec6, and Sec15 regulate DE-Cadherin trafficking from recycling endosomes to the plasma membrane.
    Dev Cell. 2005 Sep;9(3):365-76 PMID: 16224820
  36. Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12.
    Cell. 1999 Feb 5;96(3):425-36 PMID: 10025408
  37. Dedifferentiating spermatogonia outcompete somatic stem cells for niche occupancy in the Drosophila testis.
    Cell Stem Cell. 2009 Aug 7;5(2):191-203 PMID: 19664993
  38. Sara endosomes and the maintenance of Dpp signaling levels across mitosis.
    Science. 2006 Nov 17;314(5802):1135-9 PMID: 17110576
  39. Hedgehog creates a gradient of DPP activity in Drosophila wing imaginal discs.
    Mol Cell. 2000 Jan;5(1):59-71 PMID: 10678169
  40. Drosophila glypicans regulate the germline stem cell niche.
    J Cell Biol. 2009 Nov 16;187(4):473-80 PMID: 19948496
  41. The molecular signature of therapeutic mesenchymal stem cells exposes the architecture of the hematopoietic stem cell niche synapse.
    BMC Genomics. 2007 Mar 06;8:65 PMID: 17341312
  42. Mutations in Drosophila sec15 reveal a function in neuronal targeting for a subset of exocyst components.
    Neuron. 2005 Apr 21;46(2):219-32 PMID: 15848801
  43. Control of stem cell self-renewal in Drosophila spermatogenesis by JAK-STAT signaling.
    Science. 2001 Dec 21;294(5551):2546-9 PMID: 11752575
  44. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.
    Development. 1993 Jun;118(2):401-15 PMID: 8223268
  45. JAK-STAT signal inhibition regulates competition in the Drosophila testis stem cell niche.
    Science. 2009 Oct 2;326(5949):153-6 PMID: 19797664
  46. Male and female Drosophila germline stem cells: two versions of immortality.
    Science. 2007 Apr 20;316(5823):402-4 PMID: 17446390
  47. The Drosophila homolog of the Exo84 exocyst subunit promotes apical epithelial identity.
    J Cell Sci. 2007 Sep 1;120(Pt 17):3099-110 PMID: 17698923
  48. spalt encodes an evolutionarily conserved zinc finger protein of novel structure which provides homeotic gene function in the head and tail region of the Drosophila embryo.
    EMBO J. 1994 Jan 1;13(1):168-79 PMID: 7905822
  49. Molecular genetics of axis formation in zebrafish.
    Annu Rev Genet. 2005;39:561-613 PMID: 16285872
  50. Proteasomal degradation of Smad1 induced by bone morphogenetic proteins.
    J Biol Chem. 2001 Dec 7;276(49):46533-43 PMID: 11571290
  51. Parameters of growth in primary cultures and cell lines established from Drosophila imaginal discs.
    Tissue Cell. 1991;23(1):29-39 PMID: 1905427
  52. Dpp gradient formation by dynamin-dependent endocytosis: receptor trafficking and the diffusion model.
    Development. 2004 Oct;131(19):4843-56 PMID: 15358671
  53. Characterization and cloning of fasciclin III: a glycoprotein expressed on a subset of neurons and axon pathways in Drosophila.
    Cell. 1987 Mar 27;48(6):975-88 PMID: 3548998
  54. Real-time imaging of cell-cell adherens junctions reveals that Drosophila mesoderm invagination begins with two phases of apical constriction of cells.
    J Cell Sci. 2001 Feb;114(Pt 3):493-501 PMID: 11171319
  55. Rap-GEF signaling controls stem cell anchoring to their niche through regulating DE-cadherin-mediated cell adhesion in the Drosophila testis.
    Dev Cell. 2006 Jan;10(1):117-26 PMID: 16399083
  56. Mechanism of recruiting Sec6/8 (exocyst) complex to the apical junctional complex during polarization of epithelial cells.
    J Cell Sci. 2004 Feb 1;117(Pt 4):559-70 PMID: 14709721
  57. Rab11 maintains connections between germline stem cells and niche cells in the Drosophila ovary.
    Development. 2007 Oct;134(19):3413-8 PMID: 17715175
Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms1426
Published
2011-08-02
Epub
2011-00-02
Pages
415
Language
English
Region
England
NLM ID
101528555
Subset
IM
External Links
PubMed source DOI: 10.1038/ncomms1426 View journal details
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