Sigma-2 Receptor Ligand Binding Modulates Association between TSPO and TMEM97

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• The sigma-2 receptor (S2R) is implicated in diseases like cancer and neurodegenerative disorders.
• S2R is highly expressed in tumors, correlating with cell proliferation.
• TMEM97 is recently identified as the S2R, while translocator protein (TSPO) was a prior S2R candidate.

Purpose of the Study:

• To investigate the roles of TMEM97 and TSPO in S2R activity.
• To elucidate the involvement of PGRMC1, a known S2R-interacting partner.
• To explore the interaction between TMEM97, TSPO, and PGRMC1 in cancer cells.

Main Methods:

• Proximity ligation assays and co-immunoprecipitation were employed.
• Confocal microscopy was used to visualize protein colocalization.
• MCF7 breast and MIA PaCa-2 pancreatic cancer cell lines were utilized.

Main Results:

• A functional association between S2R and TSPO was demonstrated.
• TMEM97 and TSPO showed close physical colocalization in pancreatic cancer cells.
• TMEM97 ligand treatment affected TMEM97 and PGRMC1 co-immunoprecipitation with TSPO.

Conclusions:

• This study provides the first evidence of a functional interaction between TSPO and TMEM97.
• The interaction between TSPO and TMEM97 is influenced by S2R ligands.
• Findings contribute to understanding S2R function in cancer biology.