Novel role of the muskelin-RanBP9 complex as a nucleocytoplasmic mediator of cell morphology regulation

M Valiyaveettil, AA Bentley, P Gursahaney, R Hussien, R Chakravarti, N Kureishy, S Prag, JC Adams

Research output: Contribution to journalArticle (Academic Journal)peer-review

49 Citations (Scopus)

Abstract

The evolutionarily conserved kelch-repeat protein muskelin was identifi ed 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 specifi cally 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 fi ndings identify a role for muskelin – RanBP9 complex in pathways that integrate cell morphology regulation and nucleocytoplasmic communication.
Translated title of the contributionNovel role of the muskelin-RanBP9 complex as a nucleocytoplasmic mediator of cell morphology regulation
Original languageEnglish
Pages (from-to)727 - 739
Number of pages13
JournalJournal of Cell Biology
Volume182
Issue number4
DOIs
Publication statusPublished - Aug 2008

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