Beclin 1 regulates recycling endosome and is required for skin development in mice

Commun Biol. 2019 Jan 25:2:37. doi: 10.1038/s42003-018-0279-0. eCollection 2019.

Abstract

Beclin 1 is a key regulator of autophagy and endocytosis. However, its autophagy-independent functions remain poorly understood. Here, we report that Beclin 1 regulates recycling endosome and is required for skin development in vivo. We first established keratinocyte-specific Beclin 1-knockout mice and found that these mutant mice died owing to severe impairment of epidermal barrier. Beclin 1 plays a role in autophagy and the endocytic pathway in cooperation with Atg14 and UVRAG, respectively, and keratinocyte-specific Atg14-knockout mice do not show any abnormal phenotypes, suggesting that Beclin 1 has a role in skin development via the endocytic pathway. Furthermore, we found that Beclin 1 deficiency causes mislocalization of integrins via a defect of recycling endosome, abnormal cell detachment of basal cells and their immature differentiation, and abnormal skin development. These results provide the first genetic evidence showing the roles of Beclin 1 in recycling endosome and skin development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics
  • Beclin-1 / genetics*
  • Beclin-1 / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Endocytosis / genetics
  • Endosomes / metabolism*
  • Epidermis / embryology
  • Epidermis / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Mice
  • Mice, Knockout
  • Organogenesis / genetics*
  • Phenotype
  • Skin / embryology*
  • Skin / metabolism*

Substances

  • Beclin-1