CORONIN-1 AND THE RETROGRADE SIGNALING ENDOSOME

Johns Hopkins University, Baltimore MD

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Abstract

[unreadable] DESCRIPTION (provided by applicant): 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. [unreadable] [unreadable]