TFEB controls retromer expression in response to nutrient availability

Rachel Curnock, Alessia Calcagni, Andrea Ballabio, Peter J. Cullen

Research output: Contribution to journalArticle (Academic Journal)

4 Citations (Scopus)
19 Downloads (Pure)

Abstract

Endosomal recycling maintains the cell surface abundance of nutrient transporters for nutrient uptake, but how the cell integrates nutrient availability with recycling is less well understood. Here, in studying the recycling of human glutamine transporters ASCT2 (SLC1A5), LAT1 (SLC7A5), SNAT1 (SLC38A1), and SNAT2 (SLC38A2), we establish that following amino acid restriction, the adaptive delivery of SNAT2 to the cell surface relies on retromer, a master conductor of endosomal recycling. Upon complete amino acid starvation or selective glutamine depletion, we establish that retromer expression is upregulated by transcription factor EB (TFEB) and other members of the MiTF/TFE family of transcription factors through association with CLEAR elements in the promoters of the retromer genes VPS35 and VPS26A TFEB regulation of retromer expression therefore supports adaptive nutrient acquisition through endosomal recycling.

Original languageEnglish
Pages (from-to)3954-3966
Number of pages13
JournalJournal of Cell Biology
Volume218
Issue number12
DOIs
Publication statusPublished - 6 Nov 2019

Keywords

  • glutamine
  • membrane transport proteins
  • nutrients
  • staarvation
  • amino acids
  • mitf protein
  • sorting
  • transcription factor
  • genes
  • oncogenes

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