ZFYVE29 on PIP5K! Myös nimi PIKFYVE

ZFYVE29, PIKFYVE (2q34).Yllättävää! Tämä on fosfatiyyli-inositidi-kinaasi PIP5K, PIP5K3.  Asetan  Phytin- blogiini. geni ekspressoituu luuytimessä ja imusolmukkeessa.
https://www.ncbi.nlm.nih.gov/gene/200576

Also known as

CFD; FAB1; HEL37; PIP5K; PIP5K3; ZFYVE29

Summary

Phosphorylated derivatives of phosphatidylinositol (PtdIns) regulate cytoskeletal functions, membrane trafficking, and receptor signaling by recruiting protein complexes to cell- and endosomal-membranes. Humans have multiple PtdIns proteins that differ by the degree and position of phosphorylation of the inositol ring. This gene encodes an enzyme (PIKfyve; also known as phosphatidylinositol-3-phosphate 5-kinase type III or PIPKIII) that phosphorylates the D-5 position in PtdIns and phosphatidylinositol-3-phosphate (PtdIns3P) to make PtdIns5P and PtdIns(3,5)biphosphate. The D-5 position also can be phosphorylated by type I PtdIns4P-5-kinases (PIP5Ks) that are encoded by distinct genes and preferentially phosphorylate D-4 phosphorylated PtdIns. In contrast, PIKfyve preferentially phosphorylates D-3 phosphorylated PtdIns. In addition to being a lipid kinase, PIKfyve also has protein kinase activity. PIKfyve regulates endomembrane homeostasis and plays a role in the biogenesis of endosome carrier vesicles from early endosomes. Mutations in this gene cause corneal fleck dystrophy (CFD); an autosomal dominant disorder characterized by numerous small white flecks present in all layers of the corneal stroma. Histologically, these flecks appear to be keratocytes distended with lipid and mucopolysaccharide filled intracytoplasmic vacuoles. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, May 2010]

Expression

Ubiquitous expression in bone marrow (RPKM 9.7), lymph node (RPKM 8.9) and 25 other tissues See more

 Onko APP:llä fysiologinen funktio? On. Se kontrolloi PIFYVE. 

PLoS One. 2015 Jun 30;10(6):e0130485. doi: 10.1371/journal.pone.0130485. eCollection 2015.

The Amyloid Precursor Protein Controls PIKfyve Function.

Balklava Z¹, Niehage C², Currinn H¹, Mellor L³, Guscott B¹, Poulin G³, Hoflack B², Wassmer T¹.

1

Aston University, School of Life and Health Sciences, Aston Triangle, Birmingham, B4 7ET, United Kingdom.

2

Biotechnologisches Zentrum, TU-Dresden, Tatzberg 47-49, 01307 Dresden, Germany.

3

University of Manchester, Michael Smith Building, Oxford Road, Manchester, M13 9PT, United Kingdom.Abstract

While the Amyloid Precursor Protein (APP) plays a central role in Alzheimer's disease, its cellular function still remains largely unclear. It was our goal to establish APP function which will provide insights into APP's implication in Alzheimer's disease. Using our recently developed proteo-liposome assay we established the interactome of APP's intracellular domain (known as AICD), thereby identifying novel APP interactors that provide mechanistic insights into APP function. By combining biochemical, cell biological and genetic approaches we validated the functional significance of one of these novel interactors. Here we show that APP binds the PIKfyve complex, an essential kinase for the synthesis of the endosomal phosphoinositide phosphatidylinositol-3,5-bisphosphate. This signalling lipid plays a crucial role in endosomal homeostasis and receptor sorting. Loss of PIKfyve function by mutation causes profound neurodegeneration in mammals. Using C. elegans genetics we demonstrate that APP functionally cooperates with PIKfyve in vivo. This regulation is required for maintaining endosomal and neuronal function. Our findings establish an unexpected role for APP in the regulation of endosomal phosphoinositide metabolism with dramatic consequences for endosomal biology and important implications for our understanding of Alzheimer's disease.

PMID:

26125944

PMCID:

PMC4488396

DOI:

10.1371/journal.pone.0130485