Abstract
The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥99% confidence level. Using informatics, including functional annotation cluster and KEGG pathway analysis, we found great diversity of proteins involved in axonal pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate metabolism, as expected. We also found a large and complex array of proteins involved in translation, protein folding, posttranslational processing, and proteasome/ubiquitination-dependent degradation. Immunofluorescence studies performed on hippocampal neurons in culture confirmed the presence in the axonal growth cone of proteins representative of these processes. These analyses also provide evidence for rough endoplasmic reticulum and reveal a reticular structure equipped with Golgi-like functions in the axonal growth cone. Furthermore, Western blot revealed the growth cone enrichment, relative to fetal brain homogenate, of some of the proteins involved in protein synthesis, folding and catabolism. Our study provides a resource for further research and amplifies the relatively recently developed concept that the axonal growth cone is equipped with proteins capable of performing a highly diverse range of functions.
Highlights
The nerve growth cone is the enlarged leading edge of the growing neurite
growth cone particle’’ (GCP) are recovered from a discontinuous density gradient as a band that contains a large amount of cytosolic protein, and the GCPs cannot be washed by re-suspension and pelleting without disruption
Consistent with Nozumi’s data, we found enrichment in the proteome of axonal growth cone ‘‘marker’’ proteins and abundance of proteins involved in well-established growth cone functions, such as vesicular traffic and cytoskeletal remodeling
Summary
The nerve growth cone is the enlarged leading edge of the growing neurite. It is the primary site of neurite formation, which involves plasmalemmal expansion as well as cytoskeletal assembly [1,2,3]. Once the axonal growth cone has reached and recognized an appropriate target cell synaptogenesis ensues. The nerve growth cone is a developmentally regulated structure specialized for neurite assembly, amoeboid movement, detection of growth and guidance signals, and target cell recognition for synaptogenesis. As such it plays a key role in neuronal network formation and modulation during development and plasticity. The axonal growth cone has been viewed traditionally as wholly dependent on the parent neuron’s perikaryon for the supply of almost all macromolecular constituents
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