Deletion mutant of FGFR4 induces onion-like membrane structures in the nucleus

The expression of several deletion mutants of fibroblast growth factor receptor 4 (FGFR4) was studied in COS-1 cells. FGFR4-mutants lacking most of the extracellular region did not efficiently reach the plasma membrane but accumulated in the endoplasmic reticulum (ER) and Golgi body. A mutant FGFR4...

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Veröffentlicht in:Journal of cell science 2004-04, Vol.117 (Pt 9), p.1807-1819
Hauptverfasser: Sørensen, Vigdis, Brech, Andreas, Khnykin, Denis, Kolpakova, Elona, Citores, Lucia, Olsnes, Sjur
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container_end_page 1819
container_issue Pt 9
container_start_page 1807
container_title Journal of cell science
container_volume 117
creator Sørensen, Vigdis
Brech, Andreas
Khnykin, Denis
Kolpakova, Elona
Citores, Lucia
Olsnes, Sjur
description The expression of several deletion mutants of fibroblast growth factor receptor 4 (FGFR4) was studied in COS-1 cells. FGFR4-mutants lacking most of the extracellular region did not efficiently reach the plasma membrane but accumulated in the endoplasmic reticulum (ER) and Golgi body. A mutant FGFR4 lacking the kinase domain as well as most of the extracellular region (DeltaExt/R4Tth) had a distinct intracellular distribution. It localized in part to the nucleus, where it exhibited a striking spotted pattern. Ultrastructural studies showed that the nuclear spots consisted of several layers of membrane that were folded into onion-like structures at the nucleoplasmic side of the nuclear envelope. These intranuclear structures did not contain nuclear pores but were positive for the ER proteins calreticulin and protein disulfide isomerase, in addition to abundant DeltaExt/R4Tth. Formation of the intranuclear structures was sensitive to inhibition of protein kinase C. Live microscopy of a green-fluorescent-protein/DeltaExt/R4Tth fusion protein showed that the intranuclear structures were stable and immobile, suggesting that they function as deposits of the overexpressed mutant and associated membrane. The DeltaExt/R4Tth protein also induced formation of densely packed membrane stacks in the cytosol and we suggest a model were the intranuclear structures are formed by invagination of ER-derived membrane stacks into the nucleus.
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Live microscopy of a green-fluorescent-protein/DeltaExt/R4Tth fusion protein showed that the intranuclear structures were stable and immobile, suggesting that they function as deposits of the overexpressed mutant and associated membrane. 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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Company of Biologists
subjects Animals
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cell Nucleus - metabolism
Cell Nucleus - ultrastructure
COS Cells
Indoles - pharmacology
Intracellular Membranes - metabolism
Intracellular Membranes - ultrastructure
Isoquinolines - pharmacology
Maleimides - pharmacology
Microscopy, Fluorescence
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - metabolism
Protein Kinases - chemistry
Protein Kinases - deficiency
Protein Kinases - genetics
Protein Kinases - metabolism
Protein Structure, Tertiary - genetics
Receptor, Fibroblast Growth Factor, Type 4
Receptors, Fibroblast Growth Factor - chemistry
Receptors, Fibroblast Growth Factor - genetics
Receptors, Fibroblast Growth Factor - metabolism
Sequence Deletion - genetics
Staurosporine - pharmacology
Sulfonamides - pharmacology
title Deletion mutant of FGFR4 induces onion-like membrane structures in the nucleus
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