title: Calumenin-15 facilitates filopodia formation by promoting TGF-β superfamily cytokine GDF-15 transcription.
abstract: 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.
authors.affiliation: State Key Laboratory of Bio-membrane and Membrane Bio-engineering, Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Feng
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Shen
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: P
authors.initials: P
authors.lastname: Zheng
authors.forename: S
authors.initials: S
authors.lastname: Xu
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Teng
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D055436:Growth Differentiation Factor 15 / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D002135:Calcium-Binding Proteins; D047390:Casein Kinase II; D055436:Growth Differentiation Factor 15; D028884:Karyopherins; D010769:Phosphothreonine; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D016212:Transforming Growth Factor beta; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C510527:CALU protein, human; C526140:GDF15 protein, human