A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells

Heidi Hehnly, David Canton, Paula Bucko, Lorene K. Langeberg, Leah Ogier, Irwin Gelman, L. Fernando Santana, Linda Wordeman, John D. Scott

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere09384
JournaleLife
Volume4
Issue numberSeptember
DOIs
StatePublished - Sep 25 2015

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Hehnly, H., Canton, D., Bucko, P., Langeberg, L. K., Ogier, L., Gelman, I., Fernando Santana, L., Wordeman, L., & Scott, J. D. (2015). A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells. eLife, 4(September), [e09384]. https://doi.org/10.7554/eLife.09384