Centralspindlin Recruits ALIX to the Midbody during Cytokinetic Abscission in Drosophila via a Mechanism Analogous to Virus Budding

Curr Biol. 2019 Oct 21;29(20):3538-3548.e7. doi: 10.1016/j.cub.2019.09.025. Epub 2019 Oct 10.


Abscission, the final step of cytokinesis, cleaves the thin intercellular bridge connecting the two daughter cells [1-6]. The scaffold protein ALIX is a core component of the abscission machinery with an evolutionarily conserved role in midbody recruitment of ESCRT-III [7-11], which mediates the final cut [1-5, 8-10, 12-14]. In mammalian cells, the centralspindlin complex recruits the major midbody organizer CEP55 that directly binds and recruits ALIX and ESCRT-I [7-9, 15-17], which in turn cooperatively recruit ESCRT-III [8, 9, 18]. However, CEP55 is missing in Drosophila melanogaster and other invertebrates [6, 9, 19], and it is unknown how the abscission machinery is recruited to the midbody in the absence of CEP55. Here, we address how Drosophila ALIX is recruited to the midbody. Surprisingly, ALIX localizes to the midbody via its V-domain, independently of the GPPX3Y motif in the proline-rich region that recruits human ALIX [8, 9]. We elucidate that the centralspindlin component Pavarotti (H.s.MKLP1) interacts with the V-domain of ALIX to recruit it to the midbody. Specifically, our results indicate that an LxxLF motif in Pavarotti directly interacts with a conserved hydrophobic pocket in the ALIX V-domain, which in human ALIX binds (L)YPXnL/LxxLF motifs of virus proteins [20-28]. Thus, our study identifies that ALIX is recruited by an analogous mechanism during abscission in Drosophila as during virus budding in mammalian cells and an ancestral role for centralspindlin in recruiting the abscission machinery to the midbody.

Keywords: ALIX; CEP55; ESCRT-III; L-domain; LxxLF motif; Pavarotti; TSG101; abscission; centralspindlin; cytokinesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokinesis / genetics*
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Microfilament Proteins / genetics*
  • Microfilament Proteins / metabolism
  • Spindle Apparatus / physiology*


  • ALIX protein, Drosophila
  • Drosophila Proteins
  • Microfilament Proteins