Plasticity of the asialoglycoprotein receptor deciphered by ensemble FRET imaging and single-molecule counting PALM imaging

Malte Renz, Brian R. Daniels, G. Vámosi, Irwin M. Arias, Jennifer Lippincott-Schwartz

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48 Citations (Scopus)

Abstract

The stoichiometry and composition of membrane protein receptors are critical to their function. However, the inability to assess receptor subunit stoichiometry in situ has hampered efforts to relate receptor structures to functional states. Here, we address this problem for the asialoglycoprotein receptor using ensemble FRET imaging, analytical modeling, and single-molecule counting with photoactivated localization microscopy (PALM). We show that the two subunits of asialoglycoprotein receptor [rat hepatic lectin 1 (RHL1) and RHL2] can assemble into both homo- and hetero-oligomeric complexes, displaying three forms with distinct ligand specificities that coexist on the plasma membrane: higher-order homooligomers of RHL1, higher-order hetero-oligomers of RHL1 and RHL2 with two-to-one stoichiometry, and the homo-dimer RHL2 with little tendency to further homo-oligomerize. Levels of these complexes can be modulated in the plasma membrane by exogenous ligands. Thus, even a simple two-subunit receptor can exhibit remarkable plasticity in structure, and consequently function, underscoring the importance of deciphering oligomerization in single cells at the single-molecule level.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number44
DOIs
Publication statusPublished - Oct 30 2012

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Asialoglycoprotein Receptor
Microscopy
Cell Membrane
Ligands
Membrane Proteins
Single Molecule Imaging

ASJC Scopus subject areas

  • General

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Plasticity of the asialoglycoprotein receptor deciphered by ensemble FRET imaging and single-molecule counting PALM imaging. / Renz, Malte; Daniels, Brian R.; Vámosi, G.; Arias, Irwin M.; Lippincott-Schwartz, Jennifer.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 44, 30.10.2012.

Research output: Contribution to journalArticle

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