426B Poster - 05. Reproduction and gametogenesis
Friday April 08, 2:00 PM - 4:00 PM

Structural changes in centrosomes correlate with activation of a checkpoint that triggers germline stem cell loss


Authors:
Isabella Perales 1; Tingting Duan 1; Pamela Geyer 1,2

Affiliations:
1) University of Iowa; 2) NIH

Keywords:
b. oogenesis; d. centrosome

Homeostasis of Drosophila germline stem cells (GSCs) depends upon the integrity of the nuclear lamina (NL). Indeed, loss of the NL protein emerin blocks germ cell differentiation and causes GSC death due to activation of two DNA damage response kinases ATM- and Rad3-related (ATR or Mei-41) and Checkpoint kinase 2 (Chk2 or Loki). Previous studies suggested that checkpoint activation in emerin mutants results from a thickening and lobulation of the NL, due to insertion of enlarged interphase centrosomes that carry excess pericentriolar material (PCM) to nucleate microtubules. To understand whether NL distortion or centrosome structure is the primary activator of the ATR/Chk2 checkpoint, we used the Gal4-UAS system to overexpress two NL proteins, the inner nuclear membrane protein Kugelkern (Kuk) and the A-type lamin (Lamin C), chosen based on previous findings that their increased accumulation caused NL distortion. Although over-production of both proteins was achieved, only Kuk caused NL deformation in GSCs, demonstrating that Lamin C over-expression has cell type specific effects on NL structure. Whereas Kuk overexpression caused NL distortion, interphase centrosome structure was unaffected, with centrosomes localizing outside of the nuclear envelope and retaining low levels of PCM. Notably upon Kuk overexpression, GSCs were maintained and oogenesis was sustained. Based on these findings, we conclude that NL distortion alone is not sufficient for activation of the ATR/Chk2 checkpoint. Instead, our findings suggest centrosome structural changes might drive checkpoint activation in GSCs.