The low density lipoprotein receptor

摘要: The study of familial hypercholesterolemia at the molecular level has led to its advancement from a clinical syndrome fascinating experimental system. FH was first described 50 years ago by Carl Muller who concluded that disease produces high plasma cholesterol levels and myocardial infarctions in young people, is transmitted as an autosomal dominant trait determined single gene. existence two forms FH, namely heterozygous homozygous, recognized Khachadurian Fredrickson Levy much later. value model system lies availability homozygotes, because mutant genes can be studied without interference normal most important breakthrough realization defect underlying could cultured skin fibroblasts. Rapidly, LDL receptor pathway conceptualized dysfunction cells homozygotes demonstrates. Isolation protein studies on biosynthesis structure abnormal receptors cell lines provided essential groundwork for elucidation defects DNA level. power system, became nowhere more obvious than work correlated structural information with defined In addition revealing structure-function relationships polypeptide delineating mutational events, have established several general concepts. First, tight coupling binding internalization suggested endocytosis not non-specific process early observations. key finding clustered coated pits, structures had been Roth Porter 10 earlier. These investigators demonstrated, electron microscopic uptake yolk proteins mosquito oocytes, pits pinch off surface form vesicles transport extracellular fluid into cell. Studies showed directly clustering event this kind endocytosis, thus receptor-mediated distinct mechanism macromolecules across membrane. Subsequently, many additional systems defined, variations overall described.(ABSTRACT TRUNCATED AT 400 WORDS)