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Infertility is a growing concern in modern society, with 30% of cases being due to male factors, namely reduced sperm concentration, decreased motility and abnormal morphology. Sperm cells are highly compartmentalized, almost devoid of transcription and translation consequently processes such as protein phosphorylation provide a key general mechanism for(More)
Retrograde transport of several transmembrane proteins from endosomes to the trans-Golgi network (TGN) occurs via Rab 5-containing endosomes, mediated by clathrin and the recently characterized retromer complex. This complex and one of its putative sorting receptor components, SorLA, were reported to be associated to late onset Alzheimer's disease (AD). The(More)
Abeta is proteolytically produced from the Alzheimer's amyloid precursor protein (APP). Major properties attributed to Abeta include neurotoxic effects that contribute to Alzheimer's disease neurodegeneration. However, Abeta can also affect APP processing and trafficking that, in neurons, is anterogradelly transported via microtubules in a(More)
Protein phosphorylation is a critical regulatory mechanism in cellular signalling. To this end, PP1 is a major eukaryotic serine/threonine-specific phosphatase whose cellular functions, in turn, depend on complexes it forms with PP1 interacting proteins-PIPs. The importance of the testis/sperm-enriched variant, PP1γ2, in sperm motility and spermatogenesis(More)
Amyloid beta (Abeta) contributes to neurodegeneration in Alzheimer's disease and provides a close association between molecular events and pathology, although the underlying molecular mechanisms are unclear. In the work described here, Abeta did not induce amyloid precursor protein (APP) expression, but APP processing/trafficking was markedly affected. In(More)
It is now widely accepted that abnormal processing of the Alzheimer's amyloid precursor protein (APP) can contribute significantly to Alzheimer's disease (AD). APP can be processed proteolytically to give rise to several fragments, including toxic beta-amyloid (Abeta) fragments that are subsequently deposited as amyloid plaques in brains of AD patients.(More)
Mammalian sperm were previously shown to express the PP1gamma2 isoform of protein phosphatase 1 (PP1) as well as its regulatory proteins inhibitor 2 and glycogen synthase kinase 3. Furthermore, the development of sperm motility during transit through the epididymis correlates with changes in PP1 activity. Thus, since PP1 cellular activity is determined by(More)
The occurrence of consensus phosphorylation sites in the intracellular domain of the Alzheimer's amyloid precursor protein (APP), coupled with observations of their in vivo phosphorylation, prompted several workers to investigate the effects that phosphorylation of such sites could have on APP metabolism and subsequent Abeta production. However, hitherto(More)
Alzheimer's amyloid precursor protein (APP) sorting and processing are modulated through signal transduction mechanisms regulated by protein phosphorylation. Notably, protein kinase C (PKC) appears to be an important component in signaling pathways that control APP metabolism. PKCs exist in at least 11 conventional and unconventional isoforms, and PKCalpha(More)
Tyrosine 687 (Y687) of the Alzheimer's amyloid precursor protein (APP) was shown to be phosphorylated in the brains of Alzheimer's disease patients. This residue lies within a typical endocytosis consensus motif commonly found in molecules with receptor functions, strongly suggesting a potential role for APP in signal transduction. Consequently, the work(More)