CoChat
Sign Up
Cited by 53Axon Guidance and Neuronal SignalingNerve injury and regenerationNeurogenesis and neuroplasticity mechanisms

Plexin B3 promotes neurite outgrowth, interacts homophilically, and interacts with Rin

Open access
Hartwig, Christine, Veske, Andres, Krejcova, Sarka, Rosenberger, Georg, Finckh, Ulrich·2005·BMC Neuroscience
DOI 10.1186/1471-2202-6-53PMC PMC1215486
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Plexins, known to date as receptors of semaphorins, are implicated in semaphorin-mediated axon repulsion and growth cone collapse. However, subtype-specific functions of the majority of the nine members of the mammalian plexin family are largely unknown. In order to investigate functional properties of B-plexins, we analyzed the expression of human and murine plexin B3 and expressed full-length human plexins B2 (B2) and B3 (B3) in NIH-3T3 cells. Results: Unexpectedly, B3 strongly and B2 moderately stimulate neurite outgrowth of primary murine cerebellar neurons. Both plexins mediate Ca 2+/Mg 2+-dependent cell aggregation due to homophilic trans-interaction, which is strong in the case of B3 and moderate for B2. Using different deletion constructs we show that the sema domain of B3 is essential for homophilic interaction. Using yeast two-hybrid analysis, we identified the neuron-specific and calmodulin-binding Ras-related GTPase Rin as an interaction partner of the intracellular part of B3, but not of B2. Rin, also known for its neurite outgrowth-inducing characteristics, co-localizes and co-immunoprecipitates with B3 in co-transfected COS-7 cells. Conclusion: Our data suggest an involvement of homophilic interaction of B3 in semaphorin-independent signaling mechanisms positively influencing neuronal morphogenesis or function. Furthermore the neuron-specific small GTPase Rin is involved in downstream signaling of plexin B3.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/1471-2202-6-53

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PLXNB3 encodes plexin B3, which functions as a receptor for semaphorin-5A and plays a role in axon guidance, invasive growth, and cell migration.

    “PLXNB3 encodes plexin B3 which functions as a receptor for the semaphorin‐5A molecule and plays a role in axon guidance, invasive growth, and cell migration.”

    From Interstitial lung disease and pancreatic exocrine insufficiency in <scp>CADDS</scp>: Phenotypic expansion and literature review (2023) · cites this paper as [16]

    The Background (page not specified) identifies plexin B3 as interacting with semaphorin-5A and describes semaphorin-related axon repulsion, supporting the receptor and axon-guidance portions. The copy does not establish that plexin B3 plays a role in invasive growth or cell migration; the Discussion mentions migration in relation to cell-adhesion molecules more generally. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 56

  1. Dickson BJ Molecular mechanisms of axon guidance Science 2002 298 1959 1964 12471249 10.1126/science.1072165 · DOI
  2. Tessier-Lavigne M Goodman CS The molecular biology of axon guidance Science 1996 274 1123 1133 8895455 10.1126/science.274.5290.1123 · DOI
  3. Tamagnone L Artigiani S Chen H He Z Ming GI Song H Chedotal A Winberg ML Goodman CS Poo M Tessier-Lavigne M Comoglio PM Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates Cell 1999 99 71 80 10520995 10.1016/S0092-8674(00)80063-X · DOI
  4. van der Zwaag B Hellemons AJ Leenders WP Burbach JP Brunner HG Padberg GW Van Bokhoven H PLEXIN-D1, a novel plexin family member, is expressed in vascular endothelium and the central nervous system during mouse embryogenesis Dev Dyn 2002 225 336 343 12412018 10.1002/dvdy.10159 · DOI
  5. Maestrini E Tamagnone L Longati P Cremona O Gulisano M Bione S Tamanini F Neel BG Toniolo D Comoglio PM A family of transmembrane proteins with homology to the MET-hepatocyte growth factor receptor Proc Natl Acad Sci U S A 1996 93 674 678 8570614 10.1073/pnas.93.2.674 PMC40111 · DOI
  6. Pasterkamp RJ Verhaagen J Emerging roles for semaphorins in neural regeneration Brain Res Brain Res Rev 2001 35 36 54 11245885 10.1016/S0165-0173(00)00050-3 · DOI
  7. Toyofuku T Zhang H Kumanogoh A Takegahara N Suto F Kamei J Aoki K Yabuki M Hori M Fujisawa H Kikutani H Dual roles of Sema6D in cardiac morphogenesis through region-specific association of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor receptor type 2 Genes Dev 2004 18 435 447 14977921 10.1101/gad.1167304 PMC359397 · DOI
  8. Pasterkamp RJ Kolodkin AL Semaphorin junction: making tracks toward neural connectivity Curr Opin Neurobiol 2003 13 79 89 12593985 10.1016/S0959-4388(03)00003-5 · DOI
  9. Takahashi T Fournier A Nakamura F Wang LH Murakami Y Kalb RG Fujisawa H Strittmatter SM Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors Cell 1999 99 59 69 10520994 10.1016/S0092-8674(00)80062-8 · DOI
  10. Giordano S Corso S Conrotto P Artigiani S Gilestro G Barberis D Tamagnone L Comoglio PM The Semaphorin 4D receptor controls invasive growth by coupling with Met Nat Cell Biol 2002 4 720 724 12198496 10.1038/ncb843 · DOI
  11. Castellani V De Angelis E Kenwrick S Rougon G Cis and trans interactions of L1 with neuropilin-1 control axonal responses to semaphorin 3A Embo J 2002 21 6348 6357 12456642 10.1093/emboj/cdf645 PMC136949 · DOI
  12. Castellani V Chedotal A Schachner M Faivre-Sarrailh C Rougon G Analysis of the L1-deficient mouse phenotype reveals cross-talk between Sema3A and L1 signaling pathways in axonal guidance Neuron 2000 27 237 249 10985345 10.1016/S0896-6273(00)00033-7 · DOI
  13. Conrotto P Corso S Gamberini S Comoglio PM Giordano S Interplay between scatter factor receptors and B plexins controls invasive growth Oncogene 2004 23 5131 5137 15184888 10.1038/sj.onc.1207650 · DOI
  14. Swiercz JM Kuner R Offermanns S Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2 J Cell Biol 2004 165 869 880 15210733 10.1083/jcb.200312094 PMC2172401 · DOI
  15. Comeau MR Johnson R DuBose RF Petersen M Gearing P VandenBos T Park L Farrah T Buller RM Cohen JI Strockbine LD Rauch C Spriggs MK A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR Immunity 1998 8 473 482 9586637 10.1016/S1074-7613(00)80552-X · DOI
  16. Gu C Yoshida Y Livet J Reimert DV Mann F Merte J Henderson CE Jessell TM Kolodkin AL Ginty DD Semaphorin 3E and plexin-D1 control vascular pattern independently of neuropilins Science 2005 307 265 268 15550623 10.1126/science.1105416 · DOI
  17. Artigiani S Conrotto P Fazzari P Gilestro GF Barberis D Giordano S Comoglio PM Tamagnone L Plexin-B3 is a functional receptor for semaphorin 5A EMBO Rep 2004 5 710 714 15218527 10.1038/sj.embor.7400189 PMC1299100 · DOI
  18. Oster SF Bodeker MO He F Sretavan DW Invariant Sema5A inhibition serves an ensheathing function during optic nerve development Development 2003 130 775 784 12506007 10.1242/dev.00299 · DOI
  19. Oinuma I Katoh H Harada A Negishi M Direct interaction of Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by Plexin-B1 and induces cell contraction in COS-7 cells J Biol Chem 2003 278 25671 25677 12730235 10.1074/jbc.M303047200 · DOI
  20. Swiercz JM Kuner R Behrens J Offermanns S Plexin-B1 Directly Interacts with PDZ-RhoGEF/LARG to Regulate RhoA and Growth Cone Morphology Neuron 2002 35 51 63 12123608 10.1016/S0896-6273(02)00750-X · DOI
  21. Hirotani M Ohoka Y Yamamoto T Nirasawa H Furuyama T Kogo M Matsuya T Inagaki S Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors Biochem Biophys Res Commun 2002 297 32 37 12220504 10.1016/S0006-291X(02)02122-8 · DOI
  22. Perrot V Vazquez-Prado J Gutkind JS Plexin B regulates Rho through the guanine nucleotide exchange factors Leukemia-associated RhoGEF (LARG) and PDZ-RhoGEF J Biol Chem 2002 277 43115 43120 12183458 10.1074/jbc.M206005200 · DOI
  23. Driessens MH Olivo C Nagata K Inagaki M Collard JG B plexins activate Rho through PDZ-RhoGEF FEBS Lett 2002 529 168 172 12372594 10.1016/S0014-5793(02)03323-9 · DOI
  24. Aurandt J Vikis HG Gutkind JS Ahn N Guan KL The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG Proc Natl Acad Sci U S A 2002 99 12085 12090 12196628 10.1073/pnas.142433199 PMC129402 · DOI
  25. Oinuma I Ishikawa Y Katoh H Negishi M The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras Science 2004 305 862 865 15297673 10.1126/science.1097545 · DOI
  26. Artigiani S Barberis D Fazzari P Longati P Angelini P Van De Loo JW Comoglio PM Tamagnone L Functional regulation of semaphorin receptors by proprotein convertases J Biol Chem 2003 278 10094 10101 12533544 10.1074/jbc.M210156200 · DOI
  27. Williams EJ Doherty P Turner G Reid RA Hemperly JJ Walsh FS Calcium influx into neurons can solely account for cell contact-dependent neurite outgrowth stimulated by transfected L1 J Cell Biol 1992 119 883 892 1429842 10.1083/jcb.119.4.883 PMC2289701 · DOI
  28. Michelson P Hartwig C Schachner M Gal A Veske A Finckh U Missense mutations in the extracellular domain of the human neural cell adhesion molecule L1 reduce neurite outgrowth of murine cerebellar neurons Hum Mutat 2002 20 481 482 12442287 10.1002/humu.9096 · DOI
  29. Worzfeld T Puschel AW Offermanns S Kuner R Plexin-B family members demonstrate non-redundant expression patterns in the developing mouse nervous system: an anatomical basis for morphogenetic effects of Sema4D during development Eur J Neurosci 2004 19 2622 2632 15147296 10.1111/j.0953-816X.2004.03401.x · DOI
  30. Miura M Asou H Kobayashi M Uyemura K Functional expression of a full-length cDNA coding for rat neural cell adhesion molecule L1 mediates homophilic intercellular adhesion and migration of cerebellar neurons J Biol Chem 1992 267 10752 10758 1587850
  31. Calissano M Latchman DS Functional interaction between the small GTP-binding protein Rin and the N-terminal of Brn-3a transcription factor Oncogene 2003 22 5408 5414 12934100 10.1038/sj.onc.1206635 · DOI
  32. Ohta K Mizutani A Kawakami A Murakami Y Kasuya Y Takagi S Tanaka H Fujisawa H Plexin: a novel neuronal cell surface molecule that mediates cell adhesion via a homophilic binding mechanism in the presence of calcium ions Neuron 1995 14 1189 1199 7605632 10.1016/0896-6273(95)90266-X · DOI
  33. Kiryushko D Berezin V Bock E Regulators of neurite outgrowth: role of cell adhesion molecules Ann N Y Acad Sci 2004 1014 140 154 15153429 10.1196/annals.1294.015 · DOI
  34. Toyofuku T Zhang H Kumanogoh A Takegahara N Yabuki M Harada K Hori M Kikutani H Guidance of myocardial patterning in cardiac development by Sema6D reverse signalling Nat Cell Biol 2004 6 1204 1211 15543137 10.1038/ncb1193 · DOI
  35. Cheng HJ Bagri A Yaron A Stein E Pleasure SJ Tessier-Lavigne M Plexin-A3 mediates semaphorin signaling and regulates the development of hippocampal axonal projections Neuron 2001 32 249 263 11683995 10.1016/S0896-6273(01)00478-0 · DOI
  36. Perala NM Immonen T Sariola H The expression of plexins during mouse embryogenesis Gene Expr Patterns 2005 5 355 362 15661641 10.1016/j.modgep.2004.10.001 · DOI
  37. Antipenko A Himanen JP van Leyen K Nardi-Dei V Lesniak J Barton WA Rajashankar KR Lu M Hoemme C Puschel AW Nikolov DB Structure of the Semaphorin-3A Receptor Binding Module Neuron 2003 39 589 598 12925274 10.1016/S0896-6273(03)00502-6 · DOI
  38. Lemmon V Farr KL Lagenaur C L1-mediated axon outgrowth occurs via a homophilic binding mechanism Neuron 1989 2 1597 1603 2627381 10.1016/0896-6273(89)90048-2 · DOI
  39. Long H Sabatier C Ma L Plump A Yuan W Ornitz DM Tamada A Murakami F Goodman CS Tessier-Lavigne M Conserved roles for Slit and Robo proteins in midline commissural axon guidance Neuron 2004 42 213 223 15091338 10.1016/S0896-6273(04)00179-5 · DOI
  40. Hivert B Liu Z Chuang CY Doherty P Sundaresan V Robo1 and Robo2 are homophilic binding molecules that promote axonal growth Mol Cell Neurosci 2002 21 534 545 12504588 10.1006/mcne.2002.1193 · DOI
  41. Williams G Williams EJ Doherty P Dimeric versions of two short N-cadherin binding motifs (HAVDI and INPISG) function as N-cadherin agonists J Biol Chem 2002 277 4361 4367 11726665 10.1074/jbc.M109185200 · DOI
  42. Doherty P Cohen J Walsh FS Neurite outgrowth in response to transfected N-CAM changes during development and is modulated by polysialic acid Neuron 1990 5 209 219 2200449 10.1016/0896-6273(90)90310-C · DOI
  43. Sandig M Rao Y Siu CH The homophilic binding site of the neural cell adhesion molecule NCAM is directly involved in promoting neurite outgrowth from cultured neural retinal cells J Biol Chem 1994 269 14841 14848 8182092
  44. Wright JW Snyder MA Schwinof KM Combes S Copenhaver PF A role for fasciclin II in the guidance of neuronal migration Development 1999 126 3217 3228 10375511
  45. Pimenta AF Zhukareva V Barbe MF Reinoso BS Grimley C Henzel W Fischer I Levitt P The limbic system-associated membrane protein is an Ig superfamily member that mediates selective neuronal growth and axon targeting Neuron 1995 15 287 297 7646886 10.1016/0896-6273(95)90034-9 · DOI · Paper page
  46. Zhukareva V Levitt P The limbic system-associated membrane protein (LAMP) selectively mediates interactions with specific central neuron populations Development 1995 121 1161 1172 7743928
  47. DeBernardo AP Chang S Native and recombinant DM-GRASP selectively support neurite extension from neurons that express GRASP Dev Biol 1995 169 65 75 7750658 10.1006/dbio.1995.1127 · DOI
  48. Shima Y Kengaku M Hirano T Takeichi M Uemura T Regulation of dendritic maintenance and growth by a mammalian 7-pass transmembrane cadherin Dev Cell 2004 7 205 216 15296717 10.1016/j.devcel.2004.07.007 · DOI
  49. Kuja-Panula J Kiiltomaki M Yamashiro T Rouhiainen A Rauvala H AMIGO, a transmembrane protein implicated in axon tract development, defines a novel protein family with leucine-rich repeats J Cell Biol 2003 160 963 973 12629050 10.1083/jcb.200209074 PMC2173769 · DOI
  50. Araki T Zimonjic DB Popescu NC Milbrandt J Mechanism of homophilic binding mediated by ninjurin, a novel widely expressed adhesion molecule J Biol Chem 1997 272 21373 21380 9261151 10.1074/jbc.272.34.21373 · DOI
  51. Araki T Milbrandt J Ninjurin2, a novel homophilic adhesion molecule, is expressed in mature sensory and enteric neurons and promotes neurite outgrowth J Neurosci 2000 20 187 195 10627596 PMC6774113
  52. Lee CH Della NG Chew CE Zack DJ Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of ras proteins J Neurosci 1996 16 6784 6794 8824319 PMC6579259
  53. Hoshino M Nakamura S Small GTPase Rin induces neurite outgrowth through Rac/Cdc42 and calmodulin in PC12 cells J Cell Biol 2003 163 1067 1076 14662747 10.1083/jcb.200308070 PMC2173625 · DOI
  54. Itoh K Sakurai Y Asou H Umeda M Differential expression of alternatively spliced neural cell adhesion molecule L1 isoforms during oligodendrocyte maturation J Neurosci Res 2000 60 579 586 10820428 10.1002/(SICI)1097-4547(20000601)60:5<579::AID-JNR2>3.0.CO;2-# · DOI
  55. Aronheim A Zandi E Hennemann H Elledge SJ Karin M Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions Mol Cell Biol 1997 17 3094 3102 9154808 PMC232162
  56. Aronheim A Improved efficiency sos recruitment system: expression of the mammalian GAP reduces isolation of Ras GTPase false positives Nucleic Acids Res 1997 25 3373 3374 9241255 10.1093/nar/25.16.3373 PMC146875 · DOI

Cited by

Sorted by citations

Authors
Hartwig, C., Veske, A., Krejcova, S., Rosenberger, G., & Finckh, U.
Affiliations
  • Universität Hamburg (DE)
  • Tallinn University of Technology (EE)
Corresponding author
Finckh, Ulrich
ORCID
Rosenberger, Georg
Venue
BMC Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2005-08-25
Volume
6
Issue
1
Pages
53-53
ISSN
1471-2202 (ISSN-L)
DOI
10.1186/1471-2202-6-53
PMC
PMC1215486
OpenAlex
W1551253202
Cited by
53
References
0
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 3 · 2012: 5
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • BMC Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • Eesti Teadusfondi (ETF5915)
  • Bundesministerium für Bildung und Forschung (01GS0119)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
Plexin-B2, RNA integrity number, homophilic interactions, neurite outgrowth, sema domain, cell aggregation, neuronal morphogenesis, small GTPase signaling, cerebellar neurons, calmodulin-binding proteins
MeSH terms
Amino Acid Sequence, Animals, Brain, Chlorocebus aethiops, Humans, Molecular Sequence Data, Nerve Growth Factors, Nerve Tissue Proteins, Signal Transduction, Neurites, ras Proteins, Neural Cell Adhesion Molecules, COS Cells, NIH 3T3 Cells, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review