Functional characterization of two naturally occurring mutations V 221 G and T 449 N in the follicle stimulating hormone receptor
| Autor: | Bhakti R. Pathak, Antara A. Banerjee, Swati K. Achrekar, Smita D. Mahale, Shaini Joseph |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Mutation 030219 obstetrics & reproductive medicine Point mutation Mutant Biology medicine.disease_cause Biochemistry 03 medical and health sciences Transmembrane domain Follicle-stimulating hormone 030104 developmental biology 0302 clinical medicine Endocrinology Internal medicine medicine Luteinizing hormone Receptor Follicle-stimulating hormone receptor Molecular Biology hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular and Cellular Endocrinology. 440:69-79 |
| ISSN: | 0303-7207 |
| Popis: | Naturally occurring mutations in follicle stimulating hormone receptor (FSHR) affect the receptor function. Here, we characterized two such previously reported mutations, V221G and T449N, in the extracellular domain and transmembrane helix 3, of FSHR, respectively. Functional studies with the V221G mutant demonstrated an impairment in FSH binding and signaling. Validation of X-ray crystallography data indicating the contribution of FSHR specific residues in the vicinity of V221 to contribute to FSH-FSHR interaction was carried out. In vitro mutational studies showed that these residues are determinants of both FSH binding and FSH induced signaling. Analysis of the T449N mutation revealed that it results in an increase in FSH binding and high cAMP response at lower doses of FSH. A marginal hCG induced and no TSH induced cAMP production was also observed. These findings corroborated with the clinical manifestations of primary amenorrhea (V221G) and spontaneous ovarian hyperstimulation syndrome (T449N) in women harbouring these mutations. |
| Databáze: | OpenAIRE |
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