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.
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
Proc. Natl. Acad. Sci. U.S.A.
Date: Apr. 03, 2007
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