Determining The Amino Acid Sensing Specificity Of Folliculin Essay

1359 Words Sep 18th, 2016 6 Pages
Experimental Design

Aim 1: Determine the amino acid sensing specificity of folliculin. Since folliculin’s novel amino acid sensing function discovery, I plan to further understand whether FLCN specifically senses a certain amino acid and if this level of detection is enough to elicit an mTORC1 response.

1.1. Determine if folliculin’s novel molecular function in amino acid sensing is triggered by glutamine. mTORC1 activation by amino acids requires FLCN where its lysosomal residence during starvation interacts with inactive Rag complex and exerts GAP activity to activate RagC/D during amino acid re-stimulation. Active RagC/D initiates the binding between raptor and the Rag complex to promote mTORC1 lysosomal translocation and its activation. Recent discoveries in Saccharomyces cerevisiae show FLCN-FNIP orthologs, Lst7-Lst4, are necessary for amino acid-induced TORC1 activation. Similar to mammalian FLCN, Lst7-Lst4 complex is recruited to and released from the vacuolar surface upon amino acid starvation and refeeding while function as a GAP protein towards Gtr2, mammalian RagC/D ortholog (Peli-guilli et al., 2016). Yeast research revealed Lst7-Lst4 complex vacuolar dissociation and Gtr2 GAP function is stimulated by glutamine (Peli-guilli et al., 2016). Given glutamine sensitivity in yeast orthologs, I propose mammalian FLCN-FNIP complex specifically recognizes glutamine to trigger mTORC1 activation. I will observe three functional characteristics of the FLCN-FNIP complex…

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