肠上皮细胞有助于营养吸收、液体调节和病原体防御，在肠隐窝内经历持续增殖和分化，向管腔表面迁移，最终脱落。 RAB GTP 酶是细胞内囊泡运输的关键调节因子，参与各种细胞过程，包括细胞迁移和极性。在这里，我们研究了 RAB6 在肠道上皮发育和维持中的作用。我们已经培育出肠道上皮中 RAB6 被特异性删除的条件性基因敲除小鼠。我们发现 Rab6a 基因的缺失会导致胚胎死亡。在成年小鼠中，RAB6 缺失导致绒毛结构改变、连接完整性受损，但不影响顶膜和基底外侧膜域的分离。此外，RAB6 缺失会减慢细胞迁移，并对细胞增殖和干细胞维持产生不利影响。值得注意的是，RAB6 的缺失导致功能干细胞数量减少，从 Rab6a KO 小鼠中分离的隐窝在培养为 3D 类器官时快速死亡就证明了这一点。总之，这些结果强调了 RAB6 在维持肠道上皮稳态中的重要作用。© 2024。由 The Company of Biologies Ltd 出版。

Intestinal epithelial cells, instrumental in nutrient absorption, fluid regulation, and pathogen defense, undergo continuous proliferation and differentiation within the intestinal crypts, migrating towards the luminal surface where they are eventually shed. RAB GTPases are key regulators of intracellular vesicular trafficking, and are involved in various cellular processes, including cell migration and polarity. Here, we investigated the role of RAB6 in the development and maintenance of the gut epithelium. We have generated conditional knockout mice with RAB6 specifically deleted in the gut epithelium. We found that deletion of the Rab6a gene resulted in embryonic lethality. In adult mice, RAB6 depletion led to altered villi architecture, impaired junction integrity without affecting the segregation of apical and basolateral membrane domains. Further, RAB6 depletion slowed down cell migration and adversely affected both cell proliferation and stem cell maintenance. Notably, the absence of RAB6 resulted in a diminished number of functional stem cells, as evidenced by the rapid death of isolated crypts from Rab6a KO mice when cultured as 3D organoids. Together, these results underscore the essential role of RAB6 in maintaining gut epithelial homeostasis.© 2024. Published by The Company of Biologists Ltd.