Abstract
Drosophila Btk29A is the ortholog of mammalian Btk, a Tec family nonreceptor tyrosine kinase whose deficit causes X-linked agammaglobulinemia in humans. The Btk29AficP mutation induces multiple abnormalities in oogenesis, including the growth arrest of ring canals, large intercellular bridges that allow the flow of cytoplasm carrying maternal products essential for embryonic development from the nurse cells to the oocyte during oogenesis. In this study, inactivation of Parcas, a negative regulator of Btk29A, was found to promote Btk29A accumulation on ring canals with a concomitant increase in the ring canal diameter, counteracting the Btk29AficP mutation. This mutation markedly reduced the accumulation of phosphotyrosine on ring canals and in the regions of cell-cell contact, where adhesion-supporting proteins such as DE-cadherin and β-catenin ortholog Armadillo (Arm) are located. Our previous in vitro and in vivo analyses revealed that Btk29A directly phosphorylates Arm, leading to its release from DE-cadherin. In the present experiments, immunohistological analysis revealed that phosphorylation at tyrosine 150 (Y150) and Y667 of Arm was diminished in Btk29AficP mutant ring canals. Overexpression of an Arm mutant with unphosphorylatable Y150 inhibited ring canal growth. Thus Btk29A-induced Y150 phosphorylation is necessary for the normal growth of ring canals. We suggest that the dissociation of tyrosine-phosphorylated Arm from DE-cadherin allows dynamic actin to reorganize, leading to ring canal expansion and cell shape changes during the course of oogenesis.
Highlights
Bruton’s tyrosine kinase (Btk) is a member of the Tec non-receptor tyrosine kinase family, which includes Itk, Bmx, Tec, and Txk [1, 2]
We present evidence that phosphorylation of Arm Y150 and Arm Y667 by Btk29A is a critical step in the growth of ring canals, which mediate the transport of maternal materials required for embryogenesis after the fertilization of oocytes
The antibody that recognizes Y142- or Y654-phosphorylated β-catenin strongly labels Arm pY150 or pY667 associated with ring canals in a Btk29A-dependent manner (Fig. 4)
Summary
Bruton’s tyrosine kinase (Btk) is a member of the Tec non-receptor tyrosine kinase family, which includes Itk, Bmx, Tec, and Txk [1, 2]. Mutations in the Btk gene manifest as a severe immunodeficiency syndrome known as X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice [3]. Mammalian Btk is predominantly expressed in the B-cell lineage, at low levels in mature B lymphocytes and at higher levels in marrowderived hematopoietic stem cells, common lymphoid progenitor cells and developing B cells. Tyrosine-Phosphorylation of β-Catenin for Ring Canal Growth. Daiichi Sankyo Foundation of Life Science to NHK, and a Zoological MO Award from The Zoological Society of Japan to NHK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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