Cellular processing of Alzheimers amyloid precursor protein - Essay Example

Cellular processing of Alzheimer’s amyloid precursor protein This transport has been found to be Tyr653 dependent within cytoplasmic tail; what needs to be explored is cytoplasmic factors involved in the transport of APP. There exists similarity between cellular localization of green fluorescent protein-APP and endogenous APP. In MDCK cells, APP is colocalized with tetrameric APs. There is interaction between cytoplasmic tail and -adaptins. In LLC-PK1 cells, basolateral sorting of WT is restored by ectopic expression of 1B.

In LLC-PK1 cells, basolateral sorting of Y653A-GFP-APP is not restored by ectopic expression of 1B. sAPP secreted independently of targeting of the APP holoprotein. In neuronal cells, WT and Y653A-GFP-APP are distributed in a similar way. The study findings revealed localization of chimeric proteins and other intracellular compartments in MDCK cells. Antibody labelled GFP-APP-N found to be strongly associated with APP when precursor protein was found to be present as colocalized with green fluorescent protein-APP.

In MDCK cells, it was found that WT and Y653A-GFP-APP had close spatial association with AP-1. This closeness was found in the perinuclear region of the cells. As this close proximity was detected by an antibody, which is common for both AP-1A, and AP-1B so further differentiation could not be made about which complex was there. In addition to this spatial arrangement, a similar relationship was found with transferring receptors (TfnR) but no to that stronger level. An interaction was shown between 1A and 1B and cyotoplasmic domain of APP.

The strength of this interaction was different for the two domains as far as two adaptins are concerned. 1A showed similar level of interaction with WT and Y653A mutant while 1B reflected stronger interaction with WT protein as compared to Y653A mutant. In LLC-PK1 cell line, WT and Y653A-GFP-APP were found to be associated with AP-1 rather AP-1A as these cells express AP-1A exclusively. This spatial relationship was found to be stronger one. A similar association was detected between WT and Y653A-GFP-APP and AP-1B but not to that extent as for AP-1A.

In LLC-PK1 cell line, interaction between WT-GFP-APP and 1B was found to be much stronger but interaction between Y653A mutant and 1B was of low degree comparatively. In the same cells, localization of WT and Y653A-GFP-APP in relation to the surface dimension of cell was determined and it was found that they were located in the apical region. But the expression of 1B-HA influenced this localization as far as WT is concerned when it shifted to the basolateral side. In the polarized cells, secretion of GFP-sAPP was determined to be in the basolateral side.

In the neuronal cells, the distribution of both WT and Y653A-GFP-APP was found to be similar way. Contributions The results found in this study regarding the medium subunits of adaptor complexes like: AP-1A and AP-1B and their binding to cytoplasmic tail are the new discovery in the area of cell biology. Although rich information is available from the previous research studies on the issues related to transport of APP in cells and signals in the cytoplasmic tails but previous research work could not identify the actual cellular characteristics which could involve in the