Stonin1 mediates endocytosis of the proteoglycan NG2 and regulates focal adhesion dynamics and cell motility

Fabian Feutlinske, Marietta Browarski, Min-Chi Ku, Philipp Trnka, Sonia Waiczies, Thoralf Niendorf, William B. Stallcup, Rainer Glass, Eberhard Krause and Tanja Maritzen ()
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Fabian Feutlinske: Leibniz-Institut für Molekulare Pharmakologie (FMP)
Marietta Browarski: Leibniz-Institut für Molekulare Pharmakologie (FMP)
Min-Chi Ku: Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrueck Center for Molecular Medicine
Philipp Trnka: Leibniz-Institut für Molekulare Pharmakologie (FMP)
Sonia Waiczies: Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrueck Center for Molecular Medicine
Thoralf Niendorf: Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrueck Center for Molecular Medicine
William B. Stallcup: Tumor Microenvironment and Metastasis Program, Cancer Center, Sanford-Burnham Medical Research Institute
Rainer Glass: Neurosurgical Research, Clinic for Neurosurgery, Ludwig Maximilians University of Munich
Eberhard Krause: Leibniz-Institut für Molekulare Pharmakologie (FMP)
Tanja Maritzen: Leibniz-Institut für Molekulare Pharmakologie (FMP)

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms9535

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