TY - JOUR TI - A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells AU - Hehnly, Heidi AU - Canton, David AU - Bucko, Paula AU - Langeberg, Lorene K AU - Ogier, Leah AU - Gelman, Irwin AU - Santana, L Fernando AU - Wordeman, Linda AU - Scott, John D A2 - Davis, Roger VL - 4 PY - 2015 DA - 2015/09/25 SP - e09384 C1 - eLife 2015;4:e09384 DO - 10.7554/eLife.09384 UR - https://doi.org/10.7554/eLife.09384 AB - 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. KW - protein kinase KW - signal transduction KW - cell regulation KW - mitotic spindle KW - testicular cancer JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -