title: Novel role of the muskelin-RanBP9 complex as a nucleocytoplasmic mediator of cell morphology regulation.
abstract: The evolutionarily conserved kelch-repeat protein muskelin was identified as an intracellular mediator of cell spreading. We discovered that its morphological activity is controlled by association with RanBP9/RanBPM, a protein involved in transmembrane signaling and a conserved intracellular protein complex. By subcellular fractionation, endogenous muskelin is present in both the nucleus and the cytosol. Muskelin subcellular localization is coregulated by its C terminus, which provides a cytoplasmic restraint and also controls the interaction of muskelin with RanBP9, and its atypical lissencephaly-1 homology motif, which has a nuclear localization activity which is regulated by the status of the C terminus. Transient or stable short interfering RNA-based knockdown of muskelin resulted in protrusive cell morphologies with enlarged cell perimeters. Morphology was specifically restored by complementary DNAs encoding forms of muskelin with full activity of the C terminus for cytoplasmic localization and RanBP9 binding. Knockdown of RanBP9 resulted in equivalent morphological alterations. These novel findings identify a role for muskelin-RanBP9 complex in pathways that integrate cell morphology regulation and nucleocytoplasmic communication.
authors: Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors: Manojkumar
authors: M
authors: Valiyaveettil
authors: Amber A
authors: AA
authors: Bentley
authors: Priya
authors: P
authors: Gursahaney
authors: Rajaa
authors: R
authors: Hussien
authors: Ritu
authors: R
authors: Chakravarti
authors: Nina
authors: N
authors: Kureishy
authors: Soren
authors: S
authors: Prag
authors: Josephine C
authors: JC
authors: Adams
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D048430:Cell Shape; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D028884:Karyopherins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017384:Sequence Deletion; D013347:Subcellular Fractions / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D028884:Karyopherins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C503019:MKLN1 protein, human; C503020:Mkln1 protein, mouse; C116005:Ran binding protein 9