Petr Strnad

Publications (3)32.26 Total impact

• Article: Spindle positioning in human cells relies on proper centriole formation and on the microcephaly proteins CPAP and STIL.

  Daiju Kitagawa, Gregor Kohlmaier, Debora Keller, Petr Strnad, Fernando R Balestra, Isabelle Flückiger, Pierre Gönczy
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  ABSTRACT: Patients with MCPH (autosomal recessive primary microcephaly) exhibit impaired brain development, presumably due to the compromised function of neuronal progenitors. Seven MCPH loci have been identified, including one that encodes centrosome protein 4.1 associated protein (CPAP; also known as centromere protein J, CENPJ). CPAP is a large coiled-coil protein enriched at the centrosome, a structure that comprises two centrioles and surrounding pericentriolar material (PCM). CPAP depletion impairs centriole formation, whereas CPAP overexpression results in overly long centrioles. The mechanisms by which CPAP MCPH patient mutations affect brain development are not clear. Here, we identify CPAP protein domains crucial for its centriolar localization, as well as for the elongation and the formation of centrioles. Furthermore, we demonstrate that conditions that resemble CPAP MCPH patient mutations compromise centriole formation in tissue culture cells. Using adhesive micropatterns, we reveal that such defects correlate with a randomization of spindle position. Moreover, we demonstrate that the MCPH protein SCL/TAL1 interrupting locus (STIL) is also essential for centriole formation and for proper spindle position. Our findings are compatible with the notion that mutations in CPAP and STIL cause MCPH because of aberrant spindle positioning in progenitor cells during brain development.
  Journal of Cell Science 11/2011; 124(Pt 22):3884-93. · 6.11 Impact Factor
• Article: Mechanisms of procentriole formation.

  Petr Strnad, Pierre Gönczy
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  ABSTRACT: The centrosome comprises a pair of centrioles and associated pericentriolar material, and it is the principal microtubule-organizing centre of most animal cells. Like the genetic material, the centrosome is duplicated once and only once during the cell cycle. Despite the fact that both doubling events are crucial for genome integrity, the understanding of the mechanisms governing centrosome duplication has lagged behind the fuller knowledge of DNA replication. Here, we review recent findings that provide important mechanistic insights into how a single procentriole forms next to each centriole once per cell cycle, thus ensuring that one centrosome becomes two.
  Trends in cell biology 08/2008; 18(8):389-96. · 12.12 Impact Factor
• Article: Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle.

  Petr Strnad, Sebastian Leidel, Tatiana Vinogradova, Ursula Euteneuer, Alexey Khodjakov, Pierre Gönczy
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  ABSTRACT: Centrosome duplication involves the formation of a single procentriole next to each centriole, once per cell cycle. The mechanisms governing procentriole formation and those restricting its occurrence to one event per centriole are poorly understood. Here, we show that HsSAS-6 is necessary for procentriole formation and that it localizes asymmetrically next to the centriole at the onset of procentriole formation. HsSAS-6 levels oscillate during the cell cycle, with the protein being degraded in mitosis and starting to accumulate again at the end of the following G1. Our findings indicate that APC(Cdh1) targets HsSAS-6 for degradation by the 26S proteasome. Importantly, we demonstrate that increased HsSAS-6 levels promote formation of more than one procentriole per centriole. Therefore, regulated HsSAS-6 levels normally ensure that each centriole seeds the formation of a single procentriole per cell cycle, thus playing a fundamental role in driving the centrosome duplication cycle and ensuring genome integrity.
  Developmental Cell 09/2007; 13(2):203-13. · 14.03 Impact Factor