Home LiteratureArticle Details
PMID: 11035813 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The semaphorin receptor plexin-B1 specifically interacts with active Rac in a ligand-dependent manner.

Vikis HG, Li W, He Z, Guan KL

Abstract

Semaphorin molecules serve as axon guidance signals that regulate the navigation of neuronal growth cones. Semaphorins have also been implicated in other biological processes, including the immune response. Plexins, acting either alone or in complex with neuropilins, have recently been identified as functional semaphorin receptors. However, the mechanisms of signal transduction by plexins remain largely unknown. We have demonstrated a direct interaction between plexin-B1 and activated Rac. Rac specifically interacts with the cytosolic domain of plexin-B1, but not with that of plexin-A3 or -C1. Neither RhoA nor Cdc42 interacts with plexin-B1, indicating that the Rac/plexin-B1 interaction is highly specific. The binding of GTP and the integrity of the Rac effector domain are required for the interaction with plexin-B1. Furthermore, we have identified that a Cdc42/Rac interactive binding (CRIB) motif in the cytosolic domain of plexin-B1 is essential for its interaction with active Rac. We have also observed that the semaphorin CD100, a ligand for plexin-B1, stimulates the interaction between plexin-B1 and active Rac. Our results support a model by which activated Rac plays a role in mediating semaphorin signals, resulting in reorganization of actin cytoskeletal structure.

MeSH Terms
Amino Acid Motifs Antigens, CD Binding Sites Cell Line Humans Ligands Membrane Glycoproteins/metabolism Nerve Tissue Proteins/chemistry,metabolism Receptors, Cell Surface/chemistry,metabolism Semaphorins Structure-Activity Relationship rac1 GTP-Binding Protein/metabolism
Chemicals
Antigens, CD CD100 antigen Ligands Membrane Glycoproteins Nerve Tissue Proteins PLXNB1 protein, human Receptors, Cell Surface Semaphorins rac1 GTP-Binding Protein
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Vikis H G
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Li W
He Z
Guan K L
References (37)
37 references, click to expand
  1. Plexins, semaphorins, and scatter factor receptors: a common root for cell guidance signals?
    IUBMB Life. 1999 Nov;48(5):477-82 PMID: 10637762
  2. The organization of F-actin and microtubules in growth cones exposed to a brain-derived collapsing factor.
    J Cell Biol. 1993 May;121(4):867-78 PMID: 8491778
  3. The dominant negative Ras mutant, N17Ras, can inhibit signaling independently of blocking Ras activation.
    J Biol Chem. 2000 Mar 24;275(12):8854-62 PMID: 10722731
  4. Semaphorin 3A is a chemoattractant for cortical apical dendrites.
    Nature. 2000 Apr 6;404(6778):567-73 PMID: 10766232
  5. Structure of Cdc42 bound to the GTPase binding domain of PAK.
    Nat Struct Biol. 2000 May;7(5):384-8 PMID: 10802735
  6. Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones.
    Cell. 1993 Oct 22;75(2):217-27 PMID: 8402908
  7. Accumulation of actin in subsets of pioneer growth cone filopodia in response to neural and epithelial guidance cues in situ.
    J Cell Biol. 1993 Nov;123(4):935-48 PMID: 8227150
  8. The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules.
    Cell. 1993 Dec 31;75(7):1389-99 PMID: 8269517
  9. A brain serine/threonine protein kinase activated by Cdc42 and Rac1.
    Nature. 1994 Jan 6;367(6458):40-6 PMID: 8107774
  10. Purification of recombinant Rho/Rac/G25K from Escherichia coli.
    Methods Enzymol. 1995;256:3-10 PMID: 7476445
  11. A conserved binding motif defines numerous candidate target proteins for both Cdc42 and Rac GTPases.
    J Biol Chem. 1995 Dec 8;270(49):29071-4 PMID: 7493928
  12. The semaphorins: a family of axonal guidance molecules?
    Eur J Neurosci. 1996 Jul;8(7):1317-21 PMID: 8758938
  13. Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation.
    Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11780-5 PMID: 8876214
  14. The molecular biology of axon guidance.
    Science. 1996 Nov 15;274(5290):1123-33 PMID: 8895455
  15. Rac and Cdc42 induce actin polymerization and G1 cell cycle progression independently of p65PAK and the JNK/SAPK MAP kinase cascade.
    Cell. 1996 Nov 1;87(3):519-29 PMID: 8898204
  16. The crystal structure of human rac1, a member of the rho-family complexed with a GTP analogue.
    Nat Struct Biol. 1997 Feb;4(2):147-52 PMID: 9033596
  17. Alcelaphine herpesvirus type 1 has a semaphorin-like gene.
    J Gen Virol. 1995 Apr;76 ( Pt 4):1063-7 PMID: 9049359
  18. cAMP-induced switching in turning direction of nerve growth cones.
    Nature. 1997 Jul 17;388(6639):275-9 PMID: 9230436
  19. Rac1 mediates collapsin-1-induced growth cone collapse.
    J Neurosci. 1997 Aug 15;17(16):6256-63 PMID: 9236236
  20. Neuropilin is a receptor for the axonal chemorepellent Semaphorin III.
    Cell. 1997 Aug 22;90(4):739-51 PMID: 9288753
  21. Neuropilin is a semaphorin III receptor.
    Cell. 1997 Aug 22;90(4):753-62 PMID: 9288754
  22. Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III.
    Neuron. 1997 Sep;19(3):547-59 PMID: 9331348
  23. Rho GTPases and the actin cytoskeleton.
    Science. 1998 Jan 23;279(5350):509-14 PMID: 9438836
  24. Transcription of a novel mouse semaphorin gene, M-semaH, correlates with the metastatic ability of mouse tumor cell lines.
    Cancer Res. 1998 Mar 15;58(6):1238-44 PMID: 9515811
  25. A conserved negative regulatory region in alphaPAK: inhibition of PAK kinases reveals their morphological roles downstream of Cdc42 and Rac1.
    Mol Cell Biol. 1998 Apr;18(4):2153-63 PMID: 9528787
  26. A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR.
    Immunity. 1998 Apr;8(4):473-82 PMID: 9586637
  27. Rho GTPases.
    J Biol Chem. 1998 Aug 14;273(33):20685-8 PMID: 9694808
  28. Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation.
    J Biol Chem. 1998 Oct 23;273(43):28191-8 PMID: 9774440
  29. Semaphorins act as attractive and repulsive guidance signals during the development of cortical projections.
    Development. 1998 Dec;125(24):5043-53 PMID: 9811588
  30. Plexin A is a neuronal semaphorin receptor that controls axon guidance.
    Cell. 1998 Dec 23;95(7):903-16 PMID: 9875845
  31. Myelin and collapsin-1 induce motor neuron growth cone collapse through different pathways: inhibition of collapse by opposing mutants of rac1.
    J Neurosci. 1999 Mar 15;19(6):1965-75 PMID: 10066250
  32. Structure of Cdc42 in complex with the GTPase-binding domain of the 'Wiskott-Aldrich syndrome' protein.
    Nature. 1999 May 27;399(6734):379-83 PMID: 10360578
  33. Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK.
    Nature. 1999 May 27;399(6734):384-8 PMID: 10360579
  34. Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165.
    J Cell Biol. 1999 Jul 12;146(1):233-42 PMID: 10402473
  35. Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors.
    Cell. 1999 Oct 1;99(1):59-69 PMID: 10520994
  36. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates.
    Cell. 1999 Oct 1;99(1):71-80 PMID: 10520995
  37. Semaphorins and their receptors in vertebrates and invertebrates.
    Curr Opin Neurobiol. 2000 Feb;10(1):88-94 PMID: 10679438
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2000-11-07
Pages
12457-62
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18785
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com