p18/Lamtor1-mTORC1 Signaling Controls Development of Mucin-producing Goblet Cells in the Intestine

• Ito Shizuka

  Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University

• Nada Shigeyuki

  Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University

• Yamazaki Daisuke

  Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University

• Kimura Tetsuya

  Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University

• Kajiwara Kentaro

  Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University

• Miki Hiroaki

  Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka University

• Okada Masato

  Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University

抄録

Mechanistic target of rapamycin complex 1 (mTORC1) plays a pivotal role in controlling cell growth and metabolism in response to nutrients and growth factors. The activity of mTORC1 is dually regulated by amino acids and growth factor signaling, and amino acid-dependent mTORC1 activity is regulated by mTORC1 interaction with the Ragulator-Rag GTPase complex, which is localized to the surface of lysosomes via a membrane-anchored protein, p18/Lamtor1. However, the physiological function of p18-Ragulator-dependent mTORC1 signaling remains elusive. The present study evaluated the function of p18-mediated mTORC1 signaling in the intestinal epithelia using p18 conditional knockout mice. In p18 knockout colonic crypts, mTORC1 was delocalized from lysosomes, and in vivo mTORC1 activity was markedly decreased. Histologically, p18 knockout crypts exhibited significantly increased proliferating cells and dramatically decreased mucin-producing goblet cells, while overall crypt architecture and enteroendocrine cell differentiation were unaffected. Furthermore, p18 knockout crypts normally expressed transcription factors implicated in crypt differentiation, such as Cdx2 and Klf4, indicating that p18 ablation did not affect the genetic program of cell differentiation. Analysis of colon crypt organoid cultures revealed that both p18 ablation and rapamycin treatment robustly suppressed development of mucin-producing goblet cells. Hence, p18-mediated mTORC1 signaling could promote the anabolic metabolism required for robust mucin production in goblet cells to protect the intestinal epithelia from various external stressors. Key words: mTORC1, p18/lamtor1, intestinal epithelium, goblet cells, mucin

収録刊行物

• Cell Structure and Function

  Cell Structure and Function 45 (2), 93-105, 2020

  日本細胞生物学会

キーワード

• mTORC1
• p18/lamtor1
• intestinal epithelium
• goblet cells
• mucin

詳細情報

• CRID: 1390566775150425344
• NII論文ID: 130007871371
• NII書誌ID: AA0060007X
• DOI: 10.1247/csf.20018
• ISSN: 13473700
• ISSN: 03867196
• NDL書誌ID: 031311446
• PubMed: 32641600
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I031311446
• Web Site: https://www.jstage.jst.go.jp/article/csf/45/2/45_20018/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2022034680
• 本文言語コード: en
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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