title: Missing-in-metastasis MIM/MTSS1 promotes actin assembly at intercellular junctions and is required for integrity of kidney epithelia.
abstract: MIM/MTSS1 is a tissue-specific regulator of plasma membrane dynamics, whose altered expression levels have been linked to cancer metastasis. MIM deforms phosphoinositide-rich membranes through its I-BAR domain and interacts with actin monomers through its WH2 domain. Recent work proposed that MIM also potentiates Sonic hedgehog (Shh)-induced gene expression. Here, we generated MIM mutant mice and found that full-length MIM protein is dispensable for embryonic development. However, MIM-deficient mice displayed a severe urinary concentration defect caused by compromised integrity of kidney epithelia intercellular junctions, which led to bone abnormalities and end-stage renal failure. In cultured kidney epithelial (MDCK) cells, MIM displayed dynamic localization to adherens junctions, where it promoted Arp2/3-mediated actin filament assembly. This activity was dependent on the ability of MIM to interact with both membranes and actin monomers. Furthermore, results from the mouse model and cell culture experiments suggest that full-length MIM is not crucial for Shh signaling, at least during embryogenesis. Collectively, these data demonstrate that MIM modulates interplay between the actin cytoskeleton and plasma membrane to promote the maintenance of intercellular contacts in kidney epithelia.
authors.affiliation: Institute of Biotechnology, PO Box 56, University of Helsinki, 00014 Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Saarikangas
authors.forename: Pieta K
authors.initials: PK
authors.lastname: Mattila
authors.forename: Markku
authors.initials: M
authors.lastname: Varjosalo
authors.forename: Miia
authors.initials: M
authors.lastname: Bovellan
authors.forename: Janne
authors.initials: J
authors.lastname: Hakanen
authors.forename: Julia
authors.initials: J
authors.lastname: Calzada-Wack
authors.forename: Monica
authors.initials: M
authors.lastname: Tost
authors.forename: Luise
authors.initials: L
authors.lastname: Jennen
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hans
authors.forename: Marion
authors.initials: M
authors.lastname: Horsch
authors.forename: Mervi E
authors.initials: ME
authors.lastname: Hyvönen
authors.forename: Nina
authors.initials: N
authors.lastname: Perälä
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.forename: Valérie
authors.initials: V
authors.lastname: Gailus-Durner
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Martin Hrabé
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Mikko J
authors.initials: MJ
authors.lastname: Frilander
authors.forename: Harri
authors.initials: H
authors.lastname: Savilahti
authors.forename: Hannu
authors.initials: H
authors.lastname: Sariola
authors.forename: Kirsi
authors.initials: K
authors.lastname: Sainio
authors.forename: Sanna
authors.initials: S
authors.lastname: Lehtonen
authors.forename: Jussi
authors.initials: J
authors.lastname: Taipale
authors.forename: Marjo
authors.initials: M
authors.lastname: Salminen
authors.forename: Pekka
authors.initials: P
authors.lastname: Lappalainen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004285:Dogs; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D007365:Intercellular Junctions / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D000199:Actins; D008840:Microfilament Proteins; C473219:Mtss1 protein, mouse; D009363:Neoplasm Proteins