Journal article
Regulatory processes governing the cell surface expression of LH and FSH receptors
Sub-cellular biochemistry, Vol.63, pp.113-129
2012
DOI: 10.1007/978-94-007-4765-4_7
PMID: 23161136
Abstract
The LH receptor (LHR) and FSH receptor (FSHR), collectively termed the gonadotropin receptors, are members of the Family A of GPCRs. The gonadotropin receptors each contain N-linked carbohydrates that are not directly involved in hormone binding, but contribute to the proper folding, and therefore, cell surface expression of the receptor. Loss-of-function mutations of an LHR or FSHR results in decreased target cell responsiveness. Most inactivating mutations cause receptor misfolding, resulting in the retention of the mutant in its immature form in the endoplasmic reticulum. A membrane-permeable allosteric agonist of the LHR has been shown to serve as a pharmacological chaperone for misfolded and intracellularly retained LHRs by promoting their cell surface expression. Wild-type LHR and FSHR each form homodimers and heterodimers while in the ER. Therefore, when wild-type receptor is co-expressed with a misfolded mutant, the misfolded receptor dimerizes with immature wild-type receptor in the ER, causing a dominant-negative effect on cell surface expression of the mature wild-type receptor. Notably, the propensity for homodimerization is not affected by the activation status of the receptor. However, within a receptor dimer, the activity of one protomer may allosterically regulate the other protomer. Therefore, the dimerization of the gonadotropin receptors appears to be an obligate process that is part of the normal itinerary for trafficking to the cell surface and, once there, the dimerized receptors allow for additional modulations of cell signaling.
Details
- Title: Subtitle
- Regulatory processes governing the cell surface expression of LH and FSH receptors
- Creators
- Deborah L Segaloff - Department of Molecular Physiology and Biophysics, The University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA, deborah-segaloff@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Sub-cellular biochemistry, Vol.63, pp.113-129
- DOI
- 10.1007/978-94-007-4765-4_7
- PMID
- 23161136
- eISBN
- 9400747659; 9789400747654
- ISSN
- 0306-0225
- eISSN
- 2542-8810
- Grant note
- DK068614 / NIDDK NIH HHS HD022196 / NICHD NIH HHS
- Language
- English
- Date published
- 2012
- Academic Unit
- Molecular Physiology and Biophysics; Obstetrics and Gynecology
- Record Identifier
- 9984083841302771
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