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Analysis of the cellular uptake and nuclear delivery of insulin‐like growth factor binding protein‐3 in human osteosarcoma cells
Author(s) -
Micutkova Lucia,
Hermann Martin,
Offterdinger Martin,
Hess Michael W.,
Matscheski Andrea,
Pircher Haymo,
Mück Christoph,
Ebner HannesLeonhard,
Laich Andreas,
FerrandoMay Elisa,
Zwerschke Werner,
Huber Lukas A.,
JansenDürr Pidder
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26149
Subject(s) - extracellular , microbiology and biotechnology , endocytic cycle , growth factor , insulin like growth factor binding protein , intracellular , biology , nuclear protein , cell nucleus , cell growth , nucleus , cytosol , extracellular matrix , cell , endocytosis , insulin like growth factor , chemistry , transcription factor , biochemistry , receptor , gene , enzyme
Insulin‐like growth factor (IGF) binding protein‐3 (IGFBP‐3) regulates cell proliferation and survival by extracellular interaction and inactivation of the growth factor IGF‐I. Beyond that, IGF‐independent actions mediated by intracellular IGFBP‐3 including nuclear‐IGFBP‐3, have also been described. We here show, using both confocal and electron microscopy and cell fractionation, that the extracellular addition of IGFBP‐3 to living cells results in rapid uptake and nuclear delivery of IGFBP‐3, by yet partly unknown mechanisms. IGFBP‐3 is internalized through a dynamin‐dependent pathway, traffics through endocytic compartments and is finally delivered into the nucleus. We observed docking of IGFBP‐3 containing structures to the nuclear envelope and found IGFBP‐3 containing dot‐like structures to permeate the nuclear envelope. In summary, our findings establish the pathway by which this tumor suppressor protein is delivered from extracellular space to the nucleus.