Human Disorders - Gpcr

The Human Perspective Disorders Associated with G Protein Coupled Receptors

Reporter: SIM, MICHELLE D. 4 Biology – 6 Seat Number 24

TABLE 1     Human Diseases Linked to the G Protein Pathway Disease

Defective G Protein

Albright's hereditary osteodystrophy and Gsα pseudohypoparathyroidisms McCune-Albright syndrome

Gsα

Pituitary, thyroid tumors(gsp oncogene)

Gsα

Adrenocortical, ovarian tumors (gip oncogene)

Giα

Combined precocious puberty and peudohypoparathyroidism

Gsα

Disease

Defective G Protein-Coupled Receptor

Familial hypocalciuric hypercalcemia

Human analogue of BoPCAR1 receptor

Neonatal severe hyperparathyroidism

Human analogue of BoPCAR1 receptor (homozygous)

Hyperthyroidism (thyroid adenomas)

Thyrotropin receptor

Familial male precocious puberty

Luteinizing hormone receptor

X-linked nephrogenic diabetes insipidus

V2 vasopressin receptor

Retinitis pigmentosa

Rhodopsin receptor

Color blindness, spectral sensitivity variations

Cone opsin receptor

Familial glucocorticoid deficiency and isolated glucocorticoid deficiency

Adrenocorticoptropic hormone (ACTH) receptor

Figure 1 A representation of a “composite” transmembrane receptor showing the approximate sites of a number of mutations responsible for causing human diseases

Mutated MSH receptor

Mutated LH receptor

Mutated ACTH receptor

• Thyroid Adenoma

     Normal thyroid consists of follicles lined by a an epithelium and filled with colloid

– somatic mutation – a type of benign thyroid tumor – results from a mutation that leads to a gain of function – Unlike normal thyroid cells, the cells of these thyroid adenomas secrete large quantities of thyroid hormone without having to be stimulated by TSH Mutated TSH receptor

Thyroid adenoma follicles contain colloid, but there is greater variability in size than normal.

• Retinitis Pigmentosa – an inherited disease – characterized by progressive degeneration of the retina and eventual blindness – can be caused by mutations in the gene that encodes rhodopsin – results from a mutation that leads to a loss of function of the encoded receptor

Mutation of rhodopsin -a light-sensitive pigment area of the retina

• Hypoparathyroidism – Mutation in the Gα subunit in the cells of the parathyroid glands, which function at a temperature of 37°C, caused the G protein to remain inactive. – The cells of the parathyroid gland could not respond to stimuli that would normally cause them to secrete parathyroid hormone Mutated LH receptor

• short stature • disproportionate shortening of the limbs • generalized obesity • round, flattened face