Ap2m1 supports tgf-β signals to promote collagen expression by inhibiting caveolin expression

Saerom Lee, Ga Eun Lim, Yong Nyun Kim, Hyeon Sook Koo, Jaegal Shim

Research output: Contribution to journalArticlepeer-review

Abstract

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 Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the µ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 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 cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.

Original languageEnglish
Article number1639
Pages (from-to)1-15
Number of pages15
JournalInternational journal of molecular sciences
Volume22
Issue number4
DOIs
Publication statusPublished - 2021 Feb 2

Bibliographical note

Funding Information:
This work was supported in part by grants from the National Cancer Center and the National Research Foundation (NCC-1610290, NCC-1810293, NCC-1810932, NCC-2110263 and NRF-2015R1D1A1A01060359).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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