Novel role of the muskelin-RanBP9 complex as a nucleocytoplasmic mediator of cell morphology regulation.
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.
Mesh Terms:
Active Transport, Cell Nucleus, Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Amino Acid Sequence, Animals, COS Cells, Cell Adhesion Molecules, Cell Nucleus, Cell Shape, Cercopithecus aethiops, Cytoskeletal Proteins, Humans, Intracellular Signaling Peptides and Proteins, Karyopherins, Mice, Molecular Sequence Data, Nuclear Localization Signals, Nuclear Proteins, Protein Binding, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear, Sequence Deletion, Subcellular Fractions
Active Transport, Cell Nucleus, Adaptor Proteins, Signal Transducing, Amino Acid Motifs, Amino Acid Sequence, Animals, COS Cells, Cell Adhesion Molecules, Cell Nucleus, Cell Shape, Cercopithecus aethiops, Cytoskeletal Proteins, Humans, Intracellular Signaling Peptides and Proteins, Karyopherins, Mice, Molecular Sequence Data, Nuclear Localization Signals, Nuclear Proteins, Protein Binding, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear, Sequence Deletion, Subcellular Fractions
J. Cell Biol.
Date: Aug. 25, 2008
PubMed ID: 18710924
View in: Pubmed Google Scholar
Download Curated Data For This Publication
165812
Switch View:
- Interactions 2