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doi: 10.1242/10.1242/jcs.00088


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Journal of Cell Science 115, 4053-4059 (2002)
Copyright © 2002 The Company of Biologists Limited
doi: 10.1242/jcs.00088


Research Article

The mitotic-spindle-associated protein astrin is essential for progression through mitosis

Jens Gruber1,*, Jens Harborth1,*, Jörg Schnabel1, Klaus Weber1 and Mechthild Hatzfeld2,{ddagger}

1 Max Planck Institute for Biophysical Chemistry, Department of Biochemistry, Am Fassberg 11 37070 Göttingen, Germany
2 Department of Biochemistry and Pathobiochemistry, Medical Faculty of the University of Halle, 06097 Halle/Saale, Germany

{ddagger} Author for correspondence (e-mail: mechthild.hatzfeld{at}medizin.uni-halle.de)

Accepted 3 August 2002

Astrin is a mitotic-spindle-associated protein expressed in most human cell lines and tissues. However, its functions in spindle organization and mitosis have not yet been determined. Sequence analysis revealed that astrin has an N-terminal globular domain and an extended coiled-coil domain. Recombinant astrin was purified and characterized by CD spectroscopy and electron microscopy. Astrin showed parallel dimers with head-stalk structures reminiscent of motor proteins, although no sequence similarities to known motor proteins were found. In physiological buffers, astrin dimers oligomerized via their globular head domains and formed aster-like structures. Silencing of astrin in HeLa cells by RNA interference resulted in growth arrest, with formation of multipolar and highly disordered spindles. Chromosomes did not congress to the spindle equator and remained dispersed. Cells depleted of astrin were normal during interphase but were unable to progress through mitosis and finally ended in apoptotic cell death. Possible functions of astrin in mitotic spindle organization are discussed.

Key words: Astrin, Coiled coil, Microtubules, Mitotic spindle, RNA interference




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