Calumenin-15 facilitates filopodia formation by promoting TGF-β superfamily cytokine GDF-15 transcription

Filopodia, which are actin-rich finger-like membrane protrusions, have an important role in cell migration and tumor metastasis. Here we identify 13 novel calumenin (Calu) isoforms (Calu 3–15) produced by alternative splicing, and find that Calu-15 promotes filopodia formation and cell migration. Calu-15 shuttles between the nucleus and cytoplasm through interacting with importin α, Ran GTPase, and Crm1. The phosphorylation of the threonine at position 73 (Thr-73) by casein kinase 2 (CK2) is essential for the nuclear import of Calu-15, and either Thr-73 mutation or inhibition of CK2 interrupts its nuclear localization. In the nucleus, Calu-15 increases the transcription of growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-β (TGF-β) superfamily, via binding to its promoter region. Furthermore, Calu-15 induces filopodia formation mediated by GDF-15. Together, we identify that Calu-15, a novel isoform of Calu with phosphorylation-dependent nuclear localization, has a critical role in promoting filopodia formation and cell migration by upregulating the GDF-15 transcription.

• Publication year

  2013

• Venue

  Cell Death and Disease

• Publication date

  2013-10-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/cddis.2013.403PMID 24136234PMCID 3920949
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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