title: Stonin1 mediates endocytosis of the proteoglycan NG2 and regulates focal adhesion dynamics and cell motility.
abstract: Cellular functions, ranging from focal adhesion (FA) dynamics and cell motility to tumour growth, are orchestrated by signals cells receive from outside via cell surface receptors. Signalling is fine-tuned by the exo-endocytic cycling of these receptors to control cellular responses such as FA dynamics, which determine cell motility. How precisely endocytosis regulates turnover of the various cell surface receptors remains unclear. Here we identify Stonin1, an endocytic adaptor of unknown function, as a regulator of FA dynamics and cell motility, and demonstrate that it facilitates the internalization of the oncogenic proteoglycan NG2, a co-receptor of integrins and platelet-derived growth factor receptor. Embryonic fibroblasts obtained from Stonin1-deficient mice display a marked surface accumulation of NG2, increased cellular signalling and defective FA disassembly as well as altered cellular motility. These data establish Stonin1 as a specific adaptor for the endocytosis of NG2 and as an important factor for FA dynamics and cell migration.
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Feutlinske
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Marietta
authors.initials: M
authors.lastname: Browarski
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrueck Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.|German Centre for Cardiovascular Research (DZHK), Partner Site, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Min-Chi
authors.initials: MC
authors.lastname: Ku
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Trnka
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrueck Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.|German Centre for Cardiovascular Research (DZHK), Partner Site, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Sonia
authors.initials: S
authors.lastname: Waiczies
authors.affiliation: Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrueck Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.|German Centre for Cardiovascular Research (DZHK), Partner Site, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Thoralf
authors.initials: T
authors.lastname: Niendorf
authors.affiliation: Tumor Microenvironment and Metastasis Program, Cancer Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Stallcup
authors.affiliation: Neurosurgical Research, Clinic for Neurosurgery, Ludwig Maximilians University of Munich, Marchionistrasse 15, 81377 Munich, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Glass
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Krause
authors.affiliation: Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Maritzen
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics*; D002853:Chromatography, Liquid; D004705:Endocytosis / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D022001:Focal Adhesions / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D038761:Photobleaching; D011509:Proteoglycans / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D035165:Transcription Factors, General / Q000235:genetics; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D000941:Antigens; D008565:Membrane Proteins; D011509:Proteoglycans; D035165:Transcription Factors, General; D000099216:Chondroitin Sulfate Proteoglycan 4; C000606976:Stonin1 protein, mouse