Membrane organization of luteinizing hormone receptors differs between actively signaling and desensitized receptors

Mary Hunzicker-Dunn; George Barisas; Jinming Song; Deborah A Roess

doi:10.1074/jbc.M306133200

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Membrane organization of luteinizing hormone receptors differs between actively signaling and desensitized receptors

Journal article

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Membrane organization of luteinizing hormone receptors differs between actively signaling and desensitized receptors

Mary Hunzicker-Dunn, George Barisas, Jinming Song and Deborah A Roess

The Journal of biological chemistry, Vol.278(44), pp.42744-42749

10/31/2003

DOI: https://doi.org/10.1074/jbc.M306133200

Handle:

https://hdl.handle.net/2376/112964

PMID: 12930832

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Abstract

Receptors, LH - chemistry

Signal Transduction

Receptors, LH - metabolism

Luminescent Measurements

Microscopy, Confocal

Animals

Time Factors

Anisotropy

Swine

Fluorescence Resonance Energy Transfer

Protein Binding

Cell Membrane - metabolism

Diffusion

Signaling by the luteinizing hormone/choriogonadotropin receptor (LHR) is of considerable interest because of its requirement for successful reproduction. Time-resolved phosphorescence anisotropy and fluorescence resonance energy transfer were used to investigate the organization of endogenous LHRs in porcine follicular membranes in two distinct signaling states, active and desensitized. Desensitized LHRs exhibited approximately 3-fold slower rotational correlation times compared with active LHRs (59 +/- 4 and 21 +/- 9 mus, respectively), suggesting that with agonist-dependent desensitization the receptors are organized into larger protein complexes. Incubation of membranes with inhibitors of LHR desensitization, such as neutralizing anti-arrestin antibodies, a synthetic peptide corresponding to the third intracellular loop of the LHR but not the corresponding scrambled peptide, or catalytically inactive ARNO, resulted in faster rotational diffusion times equivalent to those of actively signaling LHRs. Furthermore, desensitized LHRs exhibited a 2.4-fold increase in fluorescence resonance energy transfer between LHRs suggesting that the larger protein aggregates formed during desensitization contain more self-associated LHRs. These results indicate that agonist-dependent LHR desensitization precedes organization of LHRs at the cells surface into larger protein aggregates.

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Title: Membrane organization of luteinizing hormone receptors differs between actively signaling and desensitized receptors
Creators: Mary Hunzicker-Dunn - Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA. mhd@northwestern.edu
George Barisas
Jinming Song
Deborah A Roess
Publication Details: The Journal of biological chemistry, Vol.278(44), pp.42744-42749
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: R01 HD38060 / NICHD NIH HHS HD23226 / NICHD NIH HHS
Identifiers: 99900547990401842
Language: English
Resource Type: Journal article