TGFB-inducible VASN (vasorin) promotes lysosomal acidification

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Lysosomes are crucial for degradation and signal transduction, notably MTOR signaling.
• MTOR signaling regulates lysosomal acidification, impacting autophagy, metabolism, and cell survival.
• The function of the transmembrane glycoprotein VASN remains largely uncharacterized.

Purpose of the Study:

• To investigate the role of VASN in lysosomal function and its regulation.
• To elucidate the mechanism by which VASN influences lysosomal acidification.
• To determine the physiological and pathological relevance of VASN in cellular processes and disease.

Main Methods:

• Investigated VASN expression and localization in cells.
• Utilized co-immunoprecipitation and Western blotting to study protein interactions.
• Assessed the impact of VASN on lysosomal acidification, mitophagy, and cell proliferation.

Main Results:

• Vesicle-associated membrane protein-associated neuroprotein (VASN) is a TGFB-inducible protein that enhances lysosomal acidification.
• VASN interacts with MTOR and STK11IP at the lysosome, disrupting STK11IP binding to MTOR and the V-ATPase.
• VASN is essential for TGFB-induced mitophagy, erythroid differentiation, and KRAS-driven lung cancer progression.

Conclusions:

• Vesicle-associated membrane protein-associated neuroprotein (VASN) is identified as a novel regulator of lysosomal acidification.
• VASN modulates lysosomal function, impacting key cellular processes and disease.
• Targeting VASN may offer therapeutic strategies for cancers driven by mutant KRAS.