Membrane protein stoichiometry studied in intact mammalian cells

Jonge, Niels de

doi:10.22443/rms.inf.1.144

Cited by 1 publication

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“…This paper reflects the contents of the European Microscopy Society Life Science Award lecture presented in Lyon, France at Sept. 1, 2016. Parts of the text are also published as article in the magazine InFocus of the Royal Microscopy Society (de Jonge, ).…”

Section: Introductionmentioning

confidence: 99%

Membrane protein stoichiometry studied in intact mammalian cells using liquid‐phase electron microscopy

Jonge¹

2017

Journal of Microscopy

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Receptor membrane proteins in the plasma membranes of cells respond to extracellular chemical signals by conformational changes, spatial redistribution, and (re-)assembly into protein complexes, for example, into homodimers (pairs of the same protein type). The functional state of the proteins can be determined from information about how subunits are assembled into protein complexes. Stoichiometric information about the protein complex subunits, however, is generally not obtained from intact cells but from pooled material extracted from many cells, resulting in a lack of fundamental knowledge about the functioning of membrane proteins. First, functional states may dramatically differ from cell to cell on account of cell heterogeneity. Second, extracting the membrane proteins from the plasma membrane may lead to many artefacts. Liquid-phase scanning transmission electron microscopy (STEM), in short liquid STEM, is a new technique capable of determining the locations of individual membrane proteins within the intact plasma membranes of cells in liquid. Many tens of whole cells can readily be imaged. It is possible to analyse the stoichiometry of membrane proteins in single cells while accounting for heterogenic cell populations. Liquid STEM was used to image epidermal growth factor receptors in whole COS7 cells. A study of the dimerisation of the HER2 protein in breast cancer cells revealed the presence of rare cancer cells in which HER2 was in a different functional state than in the bulk cells. Stoichiometric information about receptors is essential not only for basic science but also for biomedical application because they present many important pharmaceutical targets.

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Section: Introductionmentioning

confidence: 99%

Membrane protein stoichiometry studied in intact mammalian cells using liquid‐phase electron microscopy

Jonge¹

2017

Journal of Microscopy

View full text Add to dashboard Cite

show abstract

Membrane protein stoichiometry studied in intact mammalian cells

Cited by 1 publication

References 30 publications

Membrane protein stoichiometry studied in intact mammalian cells using liquid‐phase electron microscopy

Membrane protein stoichiometry studied in intact mammalian cells using liquid‐phase electron microscopy

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