AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression.

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for revealed the mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of , the reduced TGF-β signal was significantly restored in the mutant. In conclusion, the mutation upregulated expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including by the reduced TGF-β signal influenced the cuticle formation of the mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.