Occludin

Occludin (from the Latin occludere, German: Close ) is a protein that is involved along with the proteins of the claudin family in the formation of tight junctions, which occur in epithelial cells. Tight junctions in the epithelium close spaces between the cells and protect the body against dehydration and both from external influences (eg from the acidic contents of the stomach with pH between 1 and 2). Mutations in OCLN gene are the cause of the rare Aicardi syndrome Goutières.

Discovery

Occludin was first described by the group led by Mikio Furuse and Shoichiro Tsukita 1993. They fractionated extracts from chicken liver and found a protein with a molecular mass of 55.9 kDa composed of 504 amino acids. The hydrophilicity plot, the scientists strongly resembled the protein connexin ( also four transmembrane domains near the N- terminus).

Construction

Occludin is a transmembrane protein with four transmembrane domains, which is why it can be divided into five domains, that AE (each interrupted by a transmembrane domain ) mentioned. Wherein the protein has two extracellular loops, which are both approximately equal to (each 45 amino acids), a short intracellular loop, which connects the two extracellular loops, and two long chains at the N and C terminus. The two extracellular loops are necessary to maintain the operation ( cell- compound), one of which appears to play a role in the localization of occludin in the tight junctions. The E domain ( close to the C-terminus as shown in Figure ) is located in the cytoplasm and is needed to bind the protein ZO-1. In a study with mice, the tight junctions are permeable showed Simon Bamforth and staff that a mutated occludin, which the N -terminus and the extracellular domains are missing, yet still transported to the tight junctions, but there its function can no longer exercise and.

Until now (2005) five different types of occludin were found ( type I to IV) and occludin 1B which result from different splicing of the mRNA. This could indicate that several proteins with similar characteristics (such as the claudins ) could form a occludin protein family.

Interactions

The first interaction partner of occludin were determined with ZO-1 and ZO -2. Later, the protein ZO -3 was not identified, which also enters into an interaction with occludin. It is believed that ZO-1 binds directly to occludin and connects to the actin cytoskeleton. There were still found interactions of occludin with JAM, VAP -33, JEAP and CLMP. Occludin is also very likely phosphorylated by protein kinase C (PKC ), which then alters the distribution and function of the protein in the cell ( the phosphorylated form appears to be the active form ). Future adverse Ras -like G- proteins such as RhoA and Rac -1 play a role in the regulation of occludin, as well as in the regulatory process cytokines play a role.

Swell

  • Structural protein
  • Hereditary disease - associated protein
Human Genome Organisation Proteinkinase C
613132
de