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Unc-51-like kinase 1/2-mediated endocytic processes regulate filopodia extension and branching of sensory axons.

The molecular mechanism and significance of endocytic processes involved in directional axon elongation are not well understood. The Unc-51 family of serine/threonine kinases was shown to be important for axon growth and was also linked to endocytosis, providing an entry point to study this problem. We found that mouse Unc-51-like kinase 1/2 (Ulk1/2) proteins are localized to vesicular structures in growth cones of mouse spinal sensory neurons. RNAi-mediated knockdown of Ulk1 and/or Ulk2 resulted in impaired endocytosis of nerve growth factor (NGF), excessive axon arborization, and severely stunted axon elongation. The evidence also indicates that Ulk1/2 mediates a non-clathrin-coated endocytosis in sensory growth cones. Interestingly, NGF can induce the interaction of Ulk1 with TrkA receptor complexes through promoting K63-polyubiquitination of Ulk1 and binding of Ulk1 to the scaffolding protein p62. These results and additional studies suggest that Ulk1/2 proteins regulate filopodia extension and neurite branching during sensory axon outgrowth, probably through regulating TrkA receptor trafficking and signaling.

Pubmed ID: 17389358

Authors

  • Zhou X
  • Babu JR
  • da Silva S
  • Shu Q
  • Graef IA
  • Oliver T
  • Tomoda T
  • Tani T
  • Wooten MW
  • Wang F

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

April 3, 2007

Associated Grants

  • Agency: NIDCR NIH HHS, Id: DE016550
  • Agency: NINDS NIH HHS, Id: NS33661

Mesh Terms

  • Animals
  • Axons
  • Cell Line
  • Embryo, Mammalian
  • Endocytosis
  • Fluorescent Antibody Technique, Direct
  • Ganglia, Spinal
  • Green Fluorescent Proteins
  • Growth Cones
  • Humans
  • Mice
  • Nerve Growth Factor
  • Neurites
  • Neurons, Afferent
  • Protein-Serine-Threonine Kinases
  • Pseudopodia
  • RNA Interference
  • RNA, Small Interfering
  • Receptor Cross-Talk
  • Receptor, trkA
  • Transcription Factors
  • Ubiquitin