Lecturer’s Date: Connexin degradation Introduction Connexin refers to transmembrane a family protein which is structurally related thus assembling forming gap junctions in vertebrates, every gap junction in vertebrates is made up of two connexons also referred to as hemichannels…
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This essay seeks to explain in details, the connexin degradation mechanisms of three pathways. These pathways to be discussed are: lysosomal, ubiquitin/proteasome and autophagy. Lysosomal pathway Participation of lysosomes and endocytosis in the deprivation of gap junction plaque was planned 20 years ago. This was after the examination of intracellular vesicle-like configurations which are double-membrane, similar to gap junctions in conduction of electron micrographs. This is a research which was carried out to check on how lysosomes can be a pathway to connexin degradation. This was done by looking at the effect to the half-life of the connexins in order to find out how and to which degree they do cause degradation of connexin. These structures were referred to as annular gap junctions. The first descriptions of these structures were made available by Bjorkman from the granulosa units of life of the ovarian follicle. These gap junctions have been experimented in several dissimilar cell types. They have spacing between their particles which are clearly observed in the gap junctions. They can as well be decked out with antibodies that are anti-connexin. Various approaches have been used for verification that some of these annular gap junction outline correspond to gap junctions who are internalized instead of the cross-sections of invaginations or interdigitations of gap junction plaques. The interdigitations of gap junction plaques include sequential sectioning or lack of classification of the intercellular gap by lanthanum and freeze-fracture replicas. Research also suggests that Tyr286 is as well involved in targeting Cx43 for the process of connexin degradation by the lysosomal pathway Ubiquitin/proteasome pathway Investigation on this pathway was first done by James and Eric where they give explanation on how it relates to degradation of connexins. They carried out research on degradation of the protein connexin43 in cardiomyocyte-derived cells and the E36 Chinese ovary cells. Results from the tests show that lysosome plays a minor role in the proteolysis of connexin43 while ubiquitin antibodies play a major role in the degradation of connexin43 (Laing and Beyer, 10-13). This is because when the two tests were done, it was found out that the lysosome contributes in increasing the half-life of the connexin. This gives a clear impression that lysosome helps to increase the formation of gap junction which is significant in formation of family proteins required in the body. Ubiquitin on the other hand, reduces the half-life of the connexin. This gives a clear impression that it contributes in reducing the formation of gap junction. The reduction in this case, in turn reduces the amount of family proteins formed, making it impossible for physiological processes to take place in the body as expected. Autophagy pathway This is a degradation pathway which is known to have been implicated in a number of diseases and may be stimulated by cellular stresses for instance starvation. Research shows that connexins that are cytoplasmic are cup-shaped or ring shaped and are enclosed by structures that contain autophagy-related protein which is the LC3. There are other connexins colocalized with p62, a protein that may as well serve as a freight receptor for autophagic deprivation. Starvation is one of the situations which lead to reduction of connexins.
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