Modulation of Rab GDP-Dissociation Inhibitor Trafficking and Expression by the Transmembrane Protein 59 (TMEM59)

Abstract

Transmembrane protein 59 (TMEM59) is a type I transmembrane protein. However, the characterization and functions of TMEM59 in cells are not clear. Our results showed that TMEM59 localizes to vesicular structures. Further co-localization studies illustrated that TMEM59 is mainly distributed in the lysosome and acidic vesicular. TMEM59 movement between the nucleus and cell membrane was observed in living cells expressing TMEM59–EGFP fusion proteins. In addition, cell surface transport of amyloid precursor protein (APP) was significantly inhibited by TMEM59 and increased APP levels in HEK296T cells. TMEM59 also significantly inhibits transport of Rab GDP dissociation inhibitor alpha (GDI1) and Rab GDP dissociation inhibitor beta (GDI2), and further increases expression of GDI1 and GDI2 proteins in the cytoplasm. However, TMEM59 does not affect protein expression and localization of BACE2. These results suggest that TMEM59 may be involved in the packaging of acidic vesicles, modulated transport, and processing of APP, GDI1, and GDI2.

Keywords

• TMEM59
• localization
• protein
• GDI1
• GDI2