The septin protein Nedd5 associates with both the exocyst complex and microtubules and disruption of its GTPase activity promotes aberrant neurite sprouting in PC12 cells

Neuroreport. 2003 Jan 20;14(1):31-7. doi: 10.1097/00001756-200301200-00006.

Abstract

Nedd5 is a septin protein enriched in brain and associates with the exocyst complex, a protein complex required for neurite outgrowth in neuroendocrine PC12 cells. In this study, we further investigate the association between Nedd5 and the exocyst complex as well as the role of Nedd5 in neurite outgrowth in differentiating PC12 cells. The endogenous Nedd5 is enriched at the perinuclear region in undifferentiated PC12 cells and radiates outward, from the perinuclear region toward the growth cone, upon NGF-induced PC12 neuronal differentiation. Nedd5, as well as other septin proteins, co-immunoprecipitates with the exocyst complex and tubulin from rat brain lysate. Interestingly, the over-expression of a GTPase-defective Nedd5 mutant promotes aberrant neurite sprouting in PC12 cells. These results demonstrate that Nedd5 and other septin proteins are associated with both the exocyst complex and microtubules and uncover a putative role for the Nedd5 GTPase activity in neurite outgrowth. Taken together, these findings suggest that Nedd5 may be required for polarized neurite outgrowth, perhaps, by facilitating the exocyst complex function during neuronal differentiation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Brain Chemistry
  • Cell Differentiation / drug effects
  • Cytoskeletal Proteins / analysis
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / physiology*
  • GTP Phosphohydrolases / analysis
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / physiology*
  • Guanosine Triphosphate / metabolism
  • Macromolecular Substances
  • Microtubules / chemistry*
  • Microtubules / drug effects
  • Microtubules / ultrastructure
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / physiology
  • Nerve Growth Factor / pharmacology
  • Neurites / drug effects
  • Neurites / ultrastructure*
  • Neurons / cytology
  • Nocodazole / pharmacology
  • PC12 Cells / drug effects
  • PC12 Cells / metabolism*
  • PC12 Cells / ultrastructure
  • Rats
  • Subcellular Fractions / chemistry
  • Tubulin / metabolism

Substances

  • Cytoskeletal Proteins
  • Macromolecular Substances
  • Neoplasm Proteins
  • Tubulin
  • Guanosine Triphosphate
  • Nerve Growth Factor
  • GTP Phosphohydrolases
  • Nocodazole