RILP regulates vacuolar ATPase through interaction with the V1G1 subunit

Area of Science:

• Cell Biology
• Molecular Biology
• Protein Interactions

Background:

• Rab-interacting lysosomal protein (RILP) is a Rab7 effector controlling endosomal traffic, phagosome/autophagosome maturation, and receptor degradation.
• Vacuolar ATPase (V-ATPase) is crucial for cellular processes and implicated in various human diseases.

Purpose of the Study:

• To identify novel RILP-interacting proteins.
• To elucidate the functional relationship between RILP and V-ATPase.

Main Methods:

• Protein-protein interaction studies to identify RILP interactors.
• Immunoblotting and ubiquitination assays to assess protein stability.
• V-ATPase activity assays to measure enzyme function.

Main Results:

• The V1G1 subunit of V-ATPase (ATP6V1G1) was identified as a RILP-interacting protein.
• RILP regulates V1G1 recruitment to late endosomes/lysosomes and controls its stability via proteasomal degradation.
• RILP deficiency or V1G1 expression alterations impair V-ATPase activity.

Conclusions:

• RILP directly regulates V-ATPase activity through its interaction with the V1G1 subunit.
• RILP's role in V1G1 stability and recruitment impacts overall V-ATPase function.
• Targeting RILP offers a potential strategy for controlling V-ATPase activity in disease contexts.