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.
Highlights
Beclin 1 is a key regulator of autophagy and endocytosis
Because keratin 5 (K5)-cre functions in basal cells, Beclin 1 was expected to be completely deleted from epidermal tissue, and which was confirmed by western blotting (Fig. 1a)
We addressed whether the failure of keratinocytes in the epidermis of Beclin 1 cKO mice was partly mediated by autophagy
Summary
Beclin 1 is a key regulator of autophagy and endocytosis. its autophagy-independent functions remain poorly understood. 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. Beclin 1 is a coiled-coil protein that is a well-known regulator of autophagy in mammalian cells[12,13] It is a component of the multiprotein complex phosphatidylinositol-3-kinase (PI3K) class III, which generates phosphatidylinositol-3-phosphate (PI3P), an important molecule for membrane trafficking[14]. The endocytic pathway involves distinct small vesicles, which internalize molecules from the plasma membrane (early endosomes) and recycle them back (recycling endosomes), or deliver them to lysosomes (late endosomes) Among these endosomes, Beclin 1 has been mainly reported to be involved in the regulation of early endosomes[16,17], which contain a large amount of PI3P. We demonstrate that Beclin 1 controls the location of integrins through the regulation of recycling endosomes, and is crucial for skin development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
