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 RIS Download
Animals | Autophagy-Related Protein-1 Homolog | 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