| First Author | Hehnly H | Year | 2015 |
| Journal | Elife | Volume | 4 |
| Pages | e09384 | PubMed ID | 26406118 |
| Mgi Jnum | J:227070 | Mgi Id | MGI:5699638 |
| Doi | 10.7554/eLife.09384 | Citation | Hehnly H, et al. (2015) A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells. Elife 4:e09384 |
| abstractText | Correct orientation of the mitotic spindle in stem cells underlies organogenesis. Spindle abnormalities correlate with cancer progression in germ line-derived tumors. We discover a macromolecular complex between the scaffolding protein Gravin/AKAP12 and the mitotic kinases, Aurora A and Plk1, that is down regulated in human seminoma. Depletion of Gravin correlates with an increased mitotic index and disorganization of seminiferous tubules. Biochemical, super-resolution imaging, and enzymology approaches establish that this Gravin scaffold accumulates at the mother spindle pole during metaphase. Manipulating elements of the Gravin-Aurora A-Plk1 axis prompts mitotic delay and prevents appropriate assembly of astral microtubules to promote spindle misorientation. These pathological responses are conserved in seminiferous tubules from Gravin(-/-) mice where an overabundance of Oct3/4 positive germ line stem cells displays randomized orientation of mitotic spindles. Thus, we propose that Gravin-mediated recruitment of Aurora A and Plk1 to the mother (oldest) spindle pole contributes to the fidelity of symmetric cell division. |
