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. 2021 May;63(4-5):231-248.
doi: 10.1111/dgd.12734. Epub 2021 Jun 20.

Heat shock cognate 70 genes contribute to Drosophila spermatocyte growth progression possibly through the insulin signaling pathway

Maho Azuma  1 , Tsubasa Ogata  1 , Kanta Yamazoe  1 , Yuri Tanaka  1 , Yoshihiro H Inoue  1
Affiliations

Heat shock cognate 70 genes contribute to Drosophila spermatocyte growth progression possibly through the insulin signaling pathway

Maho Azuma et al. Dev Growth Differ. 2021 May.

Abstract

Drosophila spermatocytes grow up to 25 times their original volume before the onset of male meiosis. Several insulin-like peptides and their cognate receptors (InR) are essential for the cell growth process in Drosophila. Here, we aimed to identify additional signaling pathways and other regulatory factors required for germline cell growth in Drosophila males. Spermatocyte-specific expression of the dominant-negative form of InR inhibits cell growth. Conversely, constitutively active forms of signaling factors downstream of InR suppress growth inhibition. Furthermore, hypomorphic mutations in the target of rapamycin (Tor) inhibit spermatocyte growth. These data indicate that the insulin/TOR pathway is essential for the growth of premeiotic spermatocytes. RNA interference (RNAi) screening for the identification of other novel genes associated with cell growth showed that the silencing of each of the five members of heat shock cognate 70 (Hsc70) genes significantly inhibited the process. Hsc70-silenced spermatocytes showed Akt inhibition downstream of the insulin signaling pathway. Our pleckstrin homology domain-​green fluorescent protein (PH-GFP) reporter studies indicated that PI3K remained activated in Hsc70-4-silenced cells, suggesting that the Hsc70-4 protein possibly targets Akt or Pdk1 acting downstream of PI3K. Moreover, each of the Hsc70 proteins showed different subcellular localizations. Hsc70-2 exhibited cytoplasmic colocalization with Akt in spermatocytes before nuclear entry of the kinase during the growth phase. These results indicated the involvement of Hsc70 proteins in the activation of various steps in the insulin signaling pathway, which is essential for spermatocyte growth. Our findings provide insights into the mechanism(s) that enhance signal transduction to stimulate the growth of Drosophila spermatocytes.

Keywords: Drosophila; Akt; Hsc70; cell growth; spermatocyte.

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References

REFERENCES

    1. Alvino, C. L., Ong, S. C., McNeil, K. A., Delaine, C., Booker, G. W., Wallace, J. C., & Forbes, B. E. (2011). Understanding the mechanism of insulin and insulin-like growth factor (IGF) receptor activation by IGF-II. PLoS One, 6, e27488. https://doi.org/10.1371/journal.pone.0027488
    1. Basso, A. D., Solit, D. B., Chiosis, G., Giri, B., Tsichlis, P., & Rosen, N. (2002). Akt forms an intracellular complex with heat shock Protein 90 (Hsp90) and Cdc37 and is destabilized by inhibitors of Hsp90 function. The Journal of Biological Chemistry, 277, 39858-39866. https://doi.org/10.1074/jbc.M206322200
    1. Brand, A. H., & Perrimon, N. (1994). Raf acts downstream of the EGF receptor to determine dorsoventral polarity during Drosophila oogenesis. Genes and Development, 8, 629-639. https://doi.org/10.1101/gad.8.5.629
    1. Britton, J. S., Lockwood, W. K., Li, L., Cohen, S. M., & Edgar, B. A. (2002). Drosophila’s insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Developmental Cell, 2, 239-249. https://doi.org/10.1016/S1534-5807(02)00117-X
    1. Brogiolo, W., Stocker, H., Ikeya, T., Rintelen, F., Fernandez, R., & Hafen, E. (2001). An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Current Biology, 11, 213-221. https://doi.org/10.1016/S0960-9822(01)00068-9

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