Sandbox Reserved 591: Difference between revisions
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The cytoplasmic (intracellular) domain is released by a γ-secretase-dependent mechanism. Most known binding partners of APP interact with the intracellular domain. One of the most important is the YENPTY motif which is present in the AICD. This motif is important for Clathrin-mediated endocytosis and binding to many proteins like Fe65 and JIP. It seems that the release of AICD can contribute to intracellular variations in the cytoskeleton formation or kinase localization, and might even cause indirect effects on nuclear transcription. <ref>O'Brien, Richard J. 2011. Amyloid Precursor Protein Processing and Alzheimer’s Disease. NIH. 34: 185–204. </ref> [[Image:79_app-rasmol.jpg|thumb|left|350px|APP Protein|APP Protein]] | The cytoplasmic (intracellular) domain is released by a γ-secretase-dependent mechanism. Most known binding partners of APP interact with the intracellular domain. One of the most important is the YENPTY motif which is present in the AICD. This motif is important for Clathrin-mediated endocytosis and binding to many proteins like Fe65 and JIP. It seems that the release of AICD can contribute to intracellular variations in the cytoskeleton formation or kinase localization, and might even cause indirect effects on nuclear transcription. <ref>O'Brien, Richard J. 2011. Amyloid Precursor Protein Processing and Alzheimer’s Disease. NIH. 34: 185–204. </ref> [[Image:79_app-rasmol.jpg|thumb|left|350px|APP Protein|APP Protein]] | ||
== Function == | == Function == | ||
APP controls cholesterol turnovers needed for activity in the neurons. Most studies show overexpression of APP has effects on cell growth and health. The N-terminal heparin-binding domain of APP has been shown to stimulate neurite growth and promote synaptogenesis. Studies have also revealed that APP is able to regulate stem cells. APP plays a major role in the nervous system involved with synaptic plasticity. It also is key in maintaining neuronal calcium homeostasis which is important for transmitting synapses. <ref>PMID: | APP controls cholesterol turnovers needed for activity in the neurons. Most studies show overexpression of APP has effects on cell growth and health. The N-terminal heparin-binding domain of APP has been shown to stimulate neurite growth and promote synaptogenesis. Studies have also revealed that APP is able to regulate stem cells. APP plays a major role in the nervous system involved with synaptic plasticity. It also is key in maintaining neuronal calcium homeostasis which is important for transmitting synapses. <ref>PMID:23495999</ref>. One of the earliest indications of APP function came from analyzing the growth pattern of fibroblasts in which APP levels were lessened by expression of an antisense APP construct. These cells grew slowly, but the growth retardation could be restored by treatment with APPs. Along with the pentapeptide domain (RERMS), the infusion APPs into the brain | ||
resulted in a growth of synaptic size and improved memory capabilities in animals. An RHDS motif at the C-terminius of APP seems to promote cell adhesion. Experimental evidence has determined that APP controls the presynaptic expression and action of the high affinity choline transporter. In this circumstance, loss of APP leads to abnormal positioning of the choline transporter at neuromuscular junctions which could results in cholinergic impairment and AD pathogenesis. | resulted in a growth of synaptic size and improved memory capabilities in animals. An RHDS motif at the C-terminius of APP seems to promote cell adhesion. Experimental evidence has determined that APP controls the presynaptic expression and action of the high affinity choline transporter. In this circumstance, loss of APP leads to abnormal positioning of the choline transporter at neuromuscular junctions which could results in cholinergic impairment and AD pathogenesis. | ||
== Clinical Relevance == | == Clinical Relevance == | ||
