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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS053187-03
Application #
7283829
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Mamounas, Laura
Project Start
2005-09-01
Project End
2008-08-31
Budget Start
2007-09-01
Budget End
2008-08-31
Support Year
3
Fiscal Year
2007
Total Cost
$52,048
Indirect Cost
Name
Johns Hopkins University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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