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cAMP-induced activation of protein kinase A and p190B RhoGAP mediates down-regulation of TC10 activity at the plasma membrane and neurite outgrowth.

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  • Additional Information
    • Source:
      Publisher: Blackwell Science Ltd Country of Publication: England NLM ID: 9607379 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2443 (Electronic) Linking ISSN: 13569597 NLM ISO Abbreviation: Genes Cells Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford, UK : Blackwell Science Ltd., 1996-
    • Subject Terms:
      Neuronal Outgrowth*; Cell Membrane/*metabolism ; Cyclic AMP/*pharmacology ; Cyclic AMP-Dependent Protein Kinases/*metabolism ; GTPase-Activating Proteins/*metabolism ; Gene Expression Regulation/*drug effects ; rho GTP-Binding Proteins/*antagonists & inhibitors; Animals ; Cell Differentiation/drug effects ; Cell Membrane/drug effects ; Cyclic AMP-Dependent Protein Kinases/genetics ; Down-Regulation ; GTPase-Activating Proteins/genetics ; HeLa Cells ; Humans ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; PC12 Cells ; Rats ; Signal Transduction/drug effects ; rho GTP-Binding Proteins/genetics ; rho GTP-Binding Proteins/metabolism
    • Abstract:
      Cyclic AMP plays a pivotal role in neurite growth. During outgrowth, a trafficking system supplies membrane at growth cones. However, the cAMP-induced signaling leading to the regulation of membrane trafficking remains unknown. TC10 is a Rho family GTPase that is essential for specific types of vesicular trafficking. Recent studies have shown a role of TC10 in neurite growth in NGF-treated PC12 cells. Here, we investigated a mechanical linkage between cAMP and TC10 in neuritogenesis. Plasmalemmal TC10 activity decreased abruptly after cAMP addition in neuronal cells. TC10 was locally inactivated at extending neurite tips in cAMP-treated PC12 cells. TC10 depletion led to a decrease in cAMP-induced neurite outgrowth. Constitutively active TC10 could not rescue this growth reduction, supporting our model for a role of GTP hydrolysis of TC10 in neuritogenesis by accelerating vesicle fusion. The cAMP-induced TC10 inactivation was mediated by PKA. Considering cAMP-induced RhoA inactivation, we found that p190B, but not p190A, mediated inactivation of TC10 and RhoA. Upon cAMP treatment, p190B was recruited to the plasma membrane. STEF depletion and Rac1-N17 expression reduced cAMP-induced TC10 inactivation. Together, the PKA-STEF-Rac1-p190B pathway leading to inactivation of TC10 and RhoA at the plasma membrane plays an important role in cAMP-induced neurite outgrowth.
      (© 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)
    • Contributed Indexing:
      Keywords: PKA; cAMP; FRET; RhoA; TC10; membrane trafficking; neurite outgrowth; p190B
    • Accession Number:
      0 (GTPase-Activating Proteins)
      0 (rho GTPase-activating protein)
      E0399OZS9N (Cyclic AMP)
      EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
      EC 3.6.1.- (RHOQ protein, human)
      EC 3.6.5.2 (rho GTP-Binding Proteins)
    • Publication Date:
      Date Created: 20171027 Date Completed: 20180326 Latest Revision: 20180326
    • Publication Date:
      20250114
    • Accession Number:
      10.1111/gtc.12538
    • Accession Number:
      29072354