title: Novel functions for the endocytic regulatory proteins MICAL-L1 and EHD1 in mitosis.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology and Fred and Pamela Buffet Cancer Research Center, University of Nebraska Medical Center, Omaha, NE, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Reinecke
authors.forename: Dawn
authors.initials: D
authors.lastname: Katafiasz
authors.forename: Naava
authors.initials: N
authors.lastname: Naslavsky
authors.forename: Steve
authors.initials: S
authors.lastname: Caplan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D060588:LIM Domain Proteins / Q000378:metabolism*; D008840:Microfilament Proteins; D008938:Mitosis / Q000502:physiology*; D006899:Mixed Function Oxygenases; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D000096985:Calponins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D033921:Vesicular Transport Proteins; C120700:EHD1 protein, human; C455272:MICAL1 protein, human; D000096985:Calponins
keywords: EHD1; MICAL-L1; centrosome; cytokinesis; endocytic recycling; intercellular bridge; lagging chromosomes; membrane trafficking; midbody; mitosis