Novel Functions for the Endocytic Regulatory Proteins MICAL-L1 and EHD1 in Mitosis

James B. Reinecke, Dawn Katafiasz, Naava Naslavsky, Steve Caplan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

During interphase, recycling endosomes mediate the transport of internalized cargo back to the plasma membrane. However, in mitotic cells, recycling endosomes are essential for the completion of cytokinesis, the last phase of mitosis that promotes the physical separation the two daughter cells. Despite recent advances, our understanding of the molecular determinants that regulate recycling endosome dynamics during cytokinesis remains incomplete. We have previously demonstrated that Molecule Interacting with CasL Like-1 (MICAL-L1) and C-terminal Eps15 Homology Domain protein 1 (EHD1) coordinately regulate receptor transport from tubular recycling endosomes during interphase. However, their potential roles in controlling cytokinesis had not been addressed. In this study, we show that MICAL-L1 and EHD1 regulate mitosis. Depletion of either protein resulted in increased numbers of bi-nucleated cells. We provide evidence that bi-nucleation in MICAL-L1- and EHD1-depleted cells is a consequence of impaired recycling endosome transport during late cytokinesis. However, depletion of MICAL-L1, but not EHD1, resulted in aberrant chromosome alignment and lagging chromosomes, suggesting an EHD1-independent function for MICAL-L1 earlier in mitosis. Moreover, we provide evidence that MICAL-L1 and EHD1 differentially influence microtubule dynamics during early and late mitosis. Collectively, our new data suggest several unanticipated roles for MICAL-L1 and EHD1 during the cell cycle. MICAL-L1 and EHD1 mediate recycling endosome transport during cytokinesis. Depletion of MICAL-L1 or EHD1 leads to bi-nucleation and/or multi-nucleation. In addition to regulating cytokinesis, MICAL-L1 localizes to the mitotic spindle and regulates kinetochore fiber dynamics. Depletion of MICAL-L1 leads to hyperstabilization of kinetochore fibers, defects in chromosome alignment and lagging chromosomes.

Original languageEnglish (US)
Pages (from-to)48-67
Number of pages20
JournalTraffic
Volume16
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Centrosome
  • Cytokinesis
  • EHD1
  • Endocytic recycling
  • Intercellular bridge
  • Lagging chromosomes
  • MICAL-L1
  • Membrane trafficking
  • Midbody
  • Mitosis

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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