4.5 Article

The novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in the Drosophila gut

期刊

JOURNAL OF CELL SCIENCE
卷 134, 期 6, 页码 -

出版社

COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.257022

关键词

Drosophila; Midgut; Smooth septate junction; Epithelial cell; Intestinal stem cells

资金

  1. Japan Society for the Promotion of Science [15K07048, 19K06650]
  2. Funding Program for Next Generation, World Leading Researchers (NEXT Program) from the Japan Society for the Promotion of Science - Council for Science and Technology Policy [LS084]
  3. Grants-in-Aid for Scientific Research [15K07048, 19K06650] Funding Source: KAKEN

向作者/读者索取更多资源

A novel sSJ membrane protein, Hoka, was discovered to cooperate with other sSJ proteins to organize sSJs and maintain intestinal stem cell homeostasis through regulating aPKC and Yki activities in the Drosophila midgut.
Smooth septate junctions (sSJs) regulate the paracellular transport in the intestinal tract in arthropods. In Drosophila, the organization and physiological function of sSJs are regulated by at least three sSJ-specific membrane proteins: Ssk, Mesh and Tsp2A. Here, we report a novel sSJ membrane protein, Hoka, which has a single membrane-spanning segment with a short extracellular region, and a cytoplasmic region with Tyr-Thr-Pro-Ala motifs. The larval midgut in hoka mutants shows a defect in sSJ structure. Hoka forms a complex with Ssk, Mesh and Tsp2A, and is required for the correct localization of these proteins to sSJs. Knockdown of hoka in the adult midgut leads to intestinal barrier dysfunction and stem cell overproliferation. In hoka-knockdown midguts, aPKC is upregulated in the cytoplasm and the apical membrane of epithelial cells. The depletion of aPKC and yki in hoka-knockdown midguts results in reduced stem cell overproliferation. These findings indicate that Hoka cooperates with the sSJ proteins Ssk, Mesh and Tsp2A to organize sSJs, and is required for maintaining intestinal stem cell homeostasis through the regulation of aPKC and Yki activities in the Drosophila midgut.

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