βPix-d promotes tubulin acetylation and neurite outgrowth through a PAK/Stathmin1 signaling pathway.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Neuronal Outgrowth/*physiology ; Rho Guanine Nucleotide Exchange Factors/*metabolism ; Signal Transduction/*physiology ; Stathmin/*metabolism ; Tubulin/*metabolism ; p21-Activated Kinases/*metabolism ; rac1 GTP-Binding Protein/*metabolism; Acetylation ; Actin Cytoskeleton/metabolism ; Animals ; Cell Cycle Proteins/metabolism ; Cells, Cultured ; Female ; Hippocampus/metabolism ; Hippocampus/physiology ; Male ; Mice ; Mice, Knockout ; Microtubules/metabolism ; Neurites/metabolism ; Neurites/physiology ; Neurons/metabolism ; Neurons/physiology ; Phosphorylation/physiology ; Protein Isoforms/metabolism ; Protein Isoforms/physiology
    • Abstract:
      Microtubules are a major cytoskeletal component of neurites, and the regulation of microtubule stability is essential for neurite morphogenesis. βPix (ARHGEF7) is a guanine nucleotide exchange factor for the small GTPases Rac1 and Cdc42, which modulate the organization of actin filaments and microtubules. βPix is expressed as alternatively spliced variants, including the ubiquitous isoform βPix-a and the neuronal isoforms βPix-b and βPix-d, but the function of the neuronal isoforms remains unclear. Here, we reveal the novel role of βPix neuronal isoforms in regulating tubulin acetylation and neurite outgrowth. At DIV4, hippocampal neurons cultured from βPix neuronal isoform knockout (βPix-NIKO) mice exhibit defects in neurite morphology and tubulin acetylation, a type of tubulin modification which often labels stable microtubules. Treating βPix-NIKO neurons with paclitaxel, which stabilizes the microtubules, or reintroducing either neuronal βPix isoform to the KO neurons overcomes the impairment in neurite morphology and tubulin acetylation, suggesting that neuronal βPix isoforms may promote microtubule stabilization during neurite development. βPix-NIKO neurons also exhibit lower phosphorylation levels for Stathmin1, a microtubule-destabilizing protein, at Ser16. Expressing either βPix neuronal isoform in the βPix-NIKO neurons restores Stathmin1 phosphorylation levels, with βPix-d having a greater effect than βPix-b. Furthermore, we find that the recovery of neurite length and Stathmin1 phosphorylation via βPix-d expression requires PAK kinase activity. Taken together, our study demonstrates that βPix-d regulates the phosphorylation of Stathmin1 in a PAK-dependent manner and that neuronal βPix isoforms promote tubulin acetylation and neurite morphogenesis during neuronal development.
      Competing Interests: The authors have declared that no competing interests exist.
    • Comments:
      Erratum in: PLoS One. 2020 May 13;15(5):e0233327. (PMID: 32401784)
    • References:
      J Biol Chem. 2009 Jun 5;284(23):15640-9. (PMID: 19359244)
      Mol Cells. 2019 Aug 31;42(8):589-596. (PMID: 31402636)
      J Neurochem. 2012 Dec;123(6):904-10. (PMID: 22928776)
      Mol Cell Neurosci. 2010 Jan;43(1):15-32. (PMID: 19660553)
      Nat Protoc. 2012 Sep;7(9):1741-54. (PMID: 22936216)
      Biol Cell. 2012 Sep;104(9):533-52. (PMID: 22554054)
      Nat Rev Mol Cell Biol. 2009 May;10(5):332-43. (PMID: 19373241)
      Mol Cell Biol. 1998 Apr;18(4):2153-63. (PMID: 9528787)
      Curr Biol. 2004 Jun 8;14(11):987-95. (PMID: 15182672)
      J Neurosci. 2005 Mar 30;25(13):3379-88. (PMID: 15800193)
      Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14620-5. (PMID: 18794533)
      J Biol Chem. 2003 May 23;278(21):19220-9. (PMID: 12626503)
      J Biol Chem. 2002 Nov 15;277(46):44417-30. (PMID: 12226077)
      J Biol Chem. 2001 Jan 19;276(3):1677-80. (PMID: 11058583)
      Mol Cell Neurosci. 2016 Apr;72:9-21. (PMID: 26773468)
      Trends Cell Biol. 2015 Mar;25(3):125-36. (PMID: 25468068)
      Neuron. 2006 Sep 21;51(6):727-39. (PMID: 16982419)
      J Neurobiol. 2004 Jan;58(1):60-9. (PMID: 14598370)
      J Biol Chem. 2001 Feb 16;276(7):4948-56. (PMID: 11058585)
      J Cell Sci. 2019 Feb 25;132(5):. (PMID: 30683798)
      J Biol Chem. 1998 Dec 25;273(52):34954-60. (PMID: 9857026)
      Mol Cell Neurosci. 2012 May;50(1):10-20. (PMID: 22465229)
      Curr Biol. 1998 Mar 12;8(6):R212-4. (PMID: 9512407)
      J Cell Sci. 2017 Apr 15;130(8):1347-1353. (PMID: 28325758)
      Mol Cell Biol. 1997 Sep;17(9):5530-9. (PMID: 9271428)
      Front Cell Neurosci. 2015 Sep 09;9:343. (PMID: 26441521)
      Curr Opin Cell Biol. 2002 Feb;14(1):18-24. (PMID: 11792540)
      Cell. 2005 Nov 18;123(4):697-709. (PMID: 16286011)
      Biochem Biophys Res Commun. 1997 Jun 27;235(3):794-8. (PMID: 9207241)
      Mol Cell. 1998 Jan;1(2):183-92. (PMID: 9659915)
      FEBS Lett. 1997 Oct 20;416(2):149-52. (PMID: 9369201)
      Nat Rev Neurosci. 2000 Dec;1(3):173-80. (PMID: 11257905)
      Biochem Biophys Res Commun. 2000 Jun 16;272(3):721-5. (PMID: 10860822)
      Biochem Biophys Res Commun. 2019 Sep 3;516(4):1204-1210. (PMID: 31296385)
      J Biol Chem. 1998 Sep 11;273(37):23633-6. (PMID: 9726964)
      Science. 2011 Feb 18;331(6019):928-31. (PMID: 21273450)
      Annu Rev Pathol. 2006;1:151-70. (PMID: 18039111)
      Mol Neurodegener. 2011 Aug 30;6:64. (PMID: 21878116)
      J Biol Chem. 1996 Jun 14;271(24):14062-6. (PMID: 8662897)
      J Genet Syndr Gene Ther. 2013 Dec 6;4:203. (PMID: 24563812)
      J Cell Biol. 2008 Feb 11;180(3):619-32. (PMID: 18268107)
      Mol Cell Biol. 1997 Jun;17(6):3459-67. (PMID: 9154845)
      Sci Rep. 2018 Jun 11;8(1):8811. (PMID: 29891904)
      Synapse. 2011 Sep;65(9):971-4. (PMID: 21425351)
      J Neurosci. 1993 Feb;13(2):856-66. (PMID: 8426241)
      Neuron. 1999 Jul;23(3):569-82. (PMID: 10433268)
      J Cell Sci. 2001 Dec;114(Pt 23):4239-51. (PMID: 11739656)
      Bioarchitecture. 2013 Jul-Aug;3(4):86-109. (PMID: 24002528)
      Nat Commun. 2014 Jul 10;5:4389. (PMID: 25007915)
      Neuron. 2008 Jan 10;57(1):94-107. (PMID: 18184567)
      J Comp Neurol. 2013 Dec 15;521(18):4339-55. (PMID: 23881776)
      Genes Dev. 2005 Jan 1;19(1):1-49. (PMID: 15630019)
      J Cell Biol. 2015 Jun 8;209(5):671-86. (PMID: 26056138)
      Front Cell Neurosci. 2018 Jun 14;12:165. (PMID: 29962938)
      Nature. 1994 Jan 6;367(6458):40-6. (PMID: 8107774)
      Prog Neurobiol. 2015 Mar;126:1-18. (PMID: 25449700)
      Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):243-51. (PMID: 19526456)
      Bioessays. 2003 Jun;25(6):542-53. (PMID: 12766944)
      Mol Cells. 2001 Feb 28;11(1):89-94. (PMID: 11266127)
      Neuron. 2015 Aug 5;87(3):492-506. (PMID: 26247859)
      J Cell Sci. 2007 Apr 15;120(Pt 8):1447-56. (PMID: 17389683)
      J Biol Chem. 1999 Jan 22;274(4):2279-85. (PMID: 9890991)
      Brain Res. 1985 Nov;355(1):155-9. (PMID: 2866814)
      Am J Med Genet B Neuropsychiatr Genet. 2011 Apr;156B(3):291-302. (PMID: 21438138)
      Cytoskeleton (Hoboken). 2016 Sep;73(9):442-60. (PMID: 26887570)
    • Accession Number:
      0 (Cell Cycle Proteins)
      0 (Protein Isoforms)
      0 (Rho Guanine Nucleotide Exchange Factors)
      0 (Stathmin)
      0 (Stmn1 protein, mouse)
      0 (Tubulin)
      EC 2.7.11.1 (p21-Activated Kinases)
      EC 3.6.5.2 (rac1 GTP-Binding Protein)
    • Publication Date:
      Date Created: 20200407 Date Completed: 20200706 Latest Revision: 20200706
    • Publication Date:
      20231215
    • Accession Number:
      PMC7135283
    • Accession Number:
      10.1371/journal.pone.0230814
    • Accession Number:
      32251425