title: TFEB and the CLEAR network.
abstract: The general view of the lysosome as the terminal end of cellular catabolic pathways, has started to change due to the recent discoveries of a lysosomal nutrient sensing machinery and of a lysosome-to-nucleus signaling mechanism that modulate lysosomal function by way of the master transcriptional regulator TFEB. Lysosomal biogenesis and autophagy are coordinated by TFEB, whose function is regulated by phosphorylation. TFEB interacts with and is phosphorylated by mTORC1 at the lysosomal surface. Thus, conditions resulting in inhibition of mTOR, such as starvation and lysosomal stress, promote TFEB nuclear translocation. Preliminary evidences showing that the TFEB activation are able to ameliorate the phenotype of lysosomal storage disorders and more common neurodegenerative diseases have opened an extraordinary possibility for the development of innovative therapies. Research in TFEB and lysosomal function has continued to advance and attract interest due to increased understanding of the mechanisms behind lysosomal function. In this paper, we present a set of procedures that facilitate examination of TFEB function and its related processes.
authors: Dulbecco Telethon Institute, Pozzuoli, Italy; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA; Medical Genetics, Department of Medical and Translational Science Unit, Federico II University, Naples, Italy.
authors: Carmine
authors: C
authors: Settembre
authors: Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.
authors: Diego L
authors: DL
authors: Medina
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000502:physiology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D011506:Proteins; C064972:TFEB protein, human; C018589:lysosomal proteins
keywords: Autophagy; CLEAR network; High content screening; Lysosomal biogenesis; Lysosomal clearance; Lysosomal exocytosis; TFEB; TFEB methods; Transcriptional regulation