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ER export signals mediate plasma membrane localization of transmembrane protein TMEM72

Jiangli Ding1, Tomoh Matsumiya1,2, Yasuo Miki3

  • 1Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki University, Japan.

The FEBS Journal
|December 8, 2022
PubMed

Insights

Transmembrane protein 72 (TMEM72) is crucial for kidney development and function. This study reveals TMEM72

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Transmembrane protein 72 (TMEM72) is implicated in kidney development and renal cell carcinoma.
  • The precise function of TMEM72 remains largely uncharacterized.
  • Understanding TMEM72's role is vital for kidney disease and cancer research.

Purpose of the Study:

  • To elucidate the functional role of TMEM72 in cellular processes.
  • To investigate the structural and functional domains of TMEM72.
  • To determine TMEM72's contribution to protein transport and membrane trafficking.

Main Methods:

  • Analysis of TMEM72 structure, including transmembrane domains (TMDs) and C-terminal tail.
  • Immunofluorescence microscopy to determine TMEM72 localization.
  • Site-directed mutagenesis using deletion mutants and domain-specific replacements.
  • Unfolded protein response assays.
  • Spatial colocalization and immunoprecipitation assays.
  • Amino acid sequence analysis and immunocytochemistry.

Main Results:

  • TMEM72 possesses four transmembrane domains (TMDs) and a long C-terminal tail, localized to the plasma membrane.
  • TMDs are essential for TMEM72 folding and assembly.
  • The C-terminal region is critical for protein transport, specifically anterograde transport.
  • A specific C-terminal motif (amino acids 132-144) containing KRKKRK and APEVLA sequences is vital for efficient cellular transport and COPII association.
  • This motif appears to cooperate with membrane trafficking pathways.

Conclusions:

  • TMEM72's structural features, particularly its C-terminal region and specific motifs, are essential for its function in protein transport and membrane trafficking.
  • These findings provide insights into the molecular mechanisms underlying TMEM72's role in normal kidney development and renal cell carcinoma.
  • The study highlights the importance of TMEM72 in cellular homeostasis and suggests its potential involvement in membrane trafficking-associated diseases.
Keywords:
ER export signalTMEMTMEM72anterograde transporttransmembrane proteins

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