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SUMMARY:BioE COLLOQUIA SERIES:  "Transcriptional Regulation of Selective A
 utophagy Controls Vertebrate Development and Growth"
DTSTART:20200217T121500
DTSTAMP:20260427T221128Z
UID:e2abbeb6f4966341c3b8a680a0304257a992f2a9e2ca7b9fd59e8b4c
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Carmine Settembre\, Telethon Institute of Genetics and M
 edicine (TIGEM)\, Pozzuoli/Naples (I)\nWEEKLY BIOENGINEERING COLLOQUIA SER
 IES\n(sandwiches served)\n\nAbstract:\nOrganismal development and growth r
 ely on biosynthetic\, anabolic\, processes. Whether also degradative\, cat
 abolic\, pathways contribute to growth is still largely unknown. My labora
 tory has recently demonstrated that (macro)autophagy\, a catabolic process
  that delivers cytosolic materials to lysosome for their degradation\, pla
 ys a fundamental role in chondrocytes during bone growth (Cinque et al. Na
 ture 2015). We found that chondrocytes sustain endoplasmic reticulum (ER) 
 functions and pro-collagen secretion through the selective degradation of 
 ER fragments via autophagy (ER-phagy). In particular\, ER-phagy delivers n
 on-native\, ER-resident\, pro-collagen molecules to lysosomes through the 
 synergistic activity of the ER chaperone Calnexin (CNX) and the ER membran
 e protein FAM134B (Forrester et al. EMBO 2019).\nCurrently\, we are invest
 igating how ER-phagy is regulated in response to both metabolic and develo
 pmental cues. By combining Crispr/Cas9 technology to -omics approaches we 
 found that ER-phagy is a transcriptional-regulated process\, largely contr
 olled by TFEB and TFE3 transcription factors.  TFEB/3 induce the expressi
 on of FAM134B and promote ER-phagy activation upon prolonged nutrient star
 vation. In addition\, we discovered that this pathway is activated in chon
 drocytes by FGF signaling\, a critical regulator of bone development. FGF 
 signaling induces JNK-dependent proteasomal degradation of the insulin rec
 eptor substrate 1\, which inhibits the insulin-PI3K-PKB/Akt-mTORC1 pathway
  and promotes TFEB/TFE3 nuclear translocation and FAM134B induction. FGF s
 ignaling controls ER-phagy both in medaka fish and mouse cartilage\, hence
  suggesting that this pathway is physiologically relevant and evolutionari
 ly conserved. Thus\, our studies identify ER-phagy as new biological proce
 ss required for organismal development and growth.\n\nReferences:\nDe Leon
 ibus C\, Cinque L\, Settembre C. Emerging lysosomal pathways for quality c
 ontrol at the endoplasmic reticulum. FEBS letters 593: 2319-2329 (2019).\n
 Cinque L\, Forrester A et al. FGF signalling regulates bone growth through
  autophagy. Nature 528\, 272–275 (2015).\nForrester A\, De Leonibus C et
  al. A selective ER-phagy exerts procollagen quality control via a Calnexi
 n-FAM134B complex. EMBO J. 38\, (2019)\n\nResearch:\nThe main research int
 erest of the Settembre laboratory is to understand the regulation and the 
 role of the lysosomal-autophagy pathway in both physiological and disease 
 processes. In particular\, keeping in mind that the lysosomal-autophagy pa
 thway is dynamically regulated in response to changes in the extracellular
  environment\, the lab is exploring the hypothesis that the developmental 
 regulation of this pathway is an important contributor to organismal devel
 opment and growth. Using a combination of mouse genetics\, cell biology an
 d pharmacological approaches\, the Settembre lab has recently demonstrated
  that autophagy is induced in growing bones during post-natal development 
 and regulates the secretion of collagens\, the major components of cartila
 ge ECM. The post-natal induction of autophagy is mediated by the FGF signa
 ling\, demonstrating that growth factor signalling can promote organismal 
 growth through the activation of autophagy. The lab's studies will have th
 e potential to identify new pathways through which growth factors regulate
  cellular catabolism\, to explain how catabolic processes support anabolic
  pathways in vivo\, and to provide proof of principle that developmental d
 isorders may be treated by modulation of cellular metabolism.\n\n\nZoom li
 nk for attending remotely: https://epfl.zoom.us/j/138177026.
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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