Biology subjects

Chuykin, I.

Publications and source records attributed to Chuykin, I..

2 recordsLinked to original sources

bioRxiv2021

Frizzled3 inhibits Vangl2-Prickle3 association to establish planar cell polarity in the vertebrate neural plate

The orientation of epithelial cells in the plane of the tissue, known as planar cell polarity (PCP), is regulated by interactions of asymmetrically localized PCP protein complexes. In the Xenopus neural plate, Van Gogh-like2 (Vangl2) and Prickle3 (Pk3) proteins form a complex at the anterior cell boundaries, but how this complex is regulated in vivo remains largely unknown. Here we show that Vangl2-Pk3 association is inhibited by Frizzled3 (Fz3), a core PCP protein that is specifically expressed in the neuroectoderm and is essential for the establishment of PCP in this tissue. Proximity biotinylation and crosslinking studies revealed that the Vangl2-Pk3 interaction is suppressed by overexpressed Fz3, but enhanced in Fz3 morphants. In addition, Fz3 induced Vangl2 phosphorylation on T76 and T78, and this phosphorylation was required for Fz3-mediated inhibition of Vangl2-Pk3 complex formation. Consistent with this observation, the complex of Pk3 with nonphosphorylatable Vangl2 was not polarized in the neural plate. These findings provide evidence for in vivo regulation of the Vangl2-Pk3 complex formation and localization by a Frizzled receptor.

developmental biology↗

bioRxiv2020

Importin α7 deficiency causes infertility in male mice by disrupting spermatogenesis

Spermatogenesis is driven by an ordered series of events, which rely on trafficking of specific proteins between nucleus and cytoplasm. The importin family of proteins mediates movement of specific cargo proteins when bound to importin {beta}. Importin genes have distinct expression patterns in mouse testis, implying they may have unique roles during mammalian spermatogenesis. Here we use a loss-of-function approach to specifically determine the role of importin 7 in spermatogenesis and male fertility. We show that ablation of importin 7 in male mice leads to infertility and has multiple cumulative effects on both germ cells and Sertoli cells. Importin 7-deficient mice exhibit an impaired Sertoli cell function, including loss of Sertoli cells and a compromised nuclear transport of the androgen receptor. Furthermore, our data demonstrate devastating defects in spermiogenesis that are accompanied by disturbed histone-protamine-exchange, absence of the transcriptional regulator Brwd1 and altered expression of Rfx2 target genes, resulting in incomplete sperm maturation and massive loss of sperms. Our work uncovers the essential role of importin 7 in spermatogenesis and hence in male fertility.

developmental biology↗