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

S Noguchi, S Honda, T Saitoh, H Matsumura… - Communications …, 2019 - nature.com
S Noguchi, S Honda, T Saitoh, H Matsumura, E Nishimura, S Akira, S Shimizu
Communications biology, 2019nature.com
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 …
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.
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