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MBC in Press, published online ahead of print June 10, 2009
Mol. Biol. Cell 10.1091/mbc.E09-02-0140

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Submitted on February 17, 2009
Revised on May 22, 2009
Accepted on June 3, 2009

Stathmin Regulates Centrosomal Nucleation of Microtubules and Tubulin Dimer/Polymer Partitioning

Danielle N. Ringhoff*{dagger} and Lynne Cassimeris*

Departments of *Biological Sciences and {dagger}Chemistry, Lehigh University, Bethlehem, PA 18015

Monitoring Editor: Stephen Doxsey

Stathmin is a microtubule destabilizing protein ubiquitously expressed in vertebrates and highly expressed in many cancers. In several cell types, stathmin regulates the partitioning of tubulin between unassembled and polymer forms, but the mechanism responsible for partitioning has not been determined. We examined stathmin function in two cell systems, mouse embryo fibroblasts isolated from embryos +/+, +/- and -/- for the stathmin gene and LLCPK epithelial cells expressing stathmin-CFP or injected with stathmin protein. In MEFs, the relative amount of stathmin corresponded to genotype, where cells heterozygous for stathmin expressed half as much stathmin mRNA and protein as wild-type cells. Reduction or loss of stathmin resulted in increased microtubule polymer, but little change to microtubule dynamics at the cell periphery. Increased stathmin level in LLCPK cells, sufficient to reduce microtubule density, but allowing microtubules to remain at the cell periphery, also did not have a major impact on microtubule dynamics. In contrast, stathmin level had a significant effect on microtubule nucleation rate from centrosomes, where lower stathmin levels increased nucleation and higher stathmin levels reduced nucleation. The stathmin-dependent regulation of nucleation is only active in interphase; overexpression of stathmin-CFP did not impact metaphase microtubule nucleation rate in LLCPK cells and the number of astral microtubules was similar in stathmin +/+ and -/- MEFs. These data support a model where stathmin functions in interphase to control the partitioning of tubulins between dimer and polymer pools by setting the number of microtubules per cell.

Address correspondence to: Lynne Cassimeris (lc07{at}lehigh.edu)




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[Abstract] [Full Text] [PDF]


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