Insights into the Interaction of Lysosomal Amino Acid Transporters SLC38A9 and SLC36A1 Involved in mTORC1 Signaling in C2C12 Cells

Biomolecules. 2021 Sep 6;11(9):1314. doi: 10.3390/biom11091314.

Abstract

Amino acids are critical for mammalian target of rapamycin complex 1 (mTORC1) activation on the lysosomal surface. Amino acid transporters SLC38A9 and SLC36A1 are the members of the lysosomal amino acid sensing machinery that activates mTORC1. The current study aims to clarify the interaction of SLC38A9 and SLC36A1. Here, we discovered that leucine increased expressions of SLC38A9 and SLC36A1, leading to mTORC1 activation. SLC38A9 interacted with SLC36A1 and they enhanced each other's expression levels and locations on the lysosomal surface. Additionally, the interacting proteins of SLC38A9 in C2C12 cells were identified to participate in amino acid sensing mechanism, mTORC1 signaling pathway, and protein synthesis, which provided a resource for future investigations of skeletal muscle mass.

Keywords: SLC36A1; SLC38A9; amino acid transporter; leucine; lysosome; mTORC1 signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems / metabolism*
  • Animals
  • Cell Line
  • Leucine
  • Lysosomes / metabolism*
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Mice
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Maps
  • Signal Transduction*
  • Symporters / metabolism*
  • Up-Regulation

Substances

  • Amino Acid Transport Systems
  • SLC38A9 protein, mouse
  • Slc36a1 protein, mouse
  • Symporters
  • Mechanistic Target of Rapamycin Complex 1
  • Leucine