In this proposal we examine the role of the NGF inducible gene, coronin-1 in maintaining the fidelity of the NGF retrograde signaling endosome. Having demonstrated that coronin-1 associates with TrkA, we propose to examine the functional implications of this association. Previous reports demonstrate that in some instances coronin-1 prevents pathogenic endosomes from fusing to lysosomes thereby sustaining the life of the engulfed pathogen. This finding presents an intriguing potential function for coronin-1 in maintaining the NGF retrograde signaling endosome. Therefore, a series of experiments are proposed to determine whether coronin-1 may prevent the retrograde signaling endosome from fusing to lysosomes. We further propose experiments to analyze the implications of coronin-1 mediated regulation of endosomal stability. One such implication may be that coronin-1 provides a developing neuron with a competitive advantage over other neurons. To assess competitive advantage we will employ gain and loss of function approaches to examine whether coronin-1 can influence NGF mediated survival and competition in vitro and in vivo. We will relate findings from these experiments to the model of competition presented in the neurotrophic factor hypothesis. ? ?
| Suo, Dong; Park, Juyeon; Harrington, Anthony W et al. (2014) Coronin-1 is a neurotrophin endosomal effector that is required for developmental competition for survival. Nat Neurosci 17:36-45 |
| Deppmann, Christopher D; Mihalas, Stefan; Sharma, Nikhil et al. (2008) A model for neuronal competition during development. Science 320:369-73 |
| Deppmann, Christopher D; Alvania, Rebecca S; Taparowsky, Elizabeth J (2006) Cross-species annotation of basic leucine zipper factor interactions: Insight into the evolution of closed interaction networks. Mol Biol Evol 23:1480-92 |
