LIS1 Association with Dynactin is Required for Nuclear Motility and Genomic Union in the Fertilized Mammalian Oocyte

Christopher Payne, Justin C. St. John, João Ramalho-Santos, Gerald Schatten*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Mutations in the human LIS1 gene cause the devastating brain disorder lissencephaly. LIS1 also regulates microtubule dynamics; it interacts with the molecular motor cytoplasmic dynein and its cofactor dynactin, and is necessary for neuronal migration. Recently, LIS 1 has been suggested to mediate pronuclear migration during fertilization. Here we use rhesus monkey and bovine oocytes, as well as pronucleate-stage bovine zygotes, to determine: Lis1 RNA expression using reverse transcription-polymerase chain reaction; LIS1 protein association with dynactin using immunoprecipitation, Western blot analysis, and immunocytochemistry; and LIS1 function in mediating genomic union using antibody transfection. We find that Lis1 RNA expression increases during fertilization, that LIS1 and dynactin subunit p150/Glued co-immunoprecipitate and co-localize to pronuclear surfaces, and that anti-LIS1 antibodies transfected into zygotes dramatically inhibit pronuclear migration and apposition. LIS1 is, therefore, essential to mediate genomic union in a process that involves the dynein-dynactin complex. These results shed light on an additional role for LIS 1 and raise implications for human reproduction.

Original languageEnglish (US)
Pages (from-to)245-251
Number of pages7
JournalCell motility and the cytoskeleton
Volume56
Issue number4
DOIs
StatePublished - Dec 2003

Keywords

  • Fertilization
  • LIS1 inhibition
  • Microtubules, molecular motor
  • Nuclear movement

ASJC Scopus subject areas

  • Structural Biology
  • Cell Biology

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