Neurons and plaques of Alzheimer's disease patients highly express the neuronal membrane docking protein p42IP4/centaurin alpha.
The protein p42(IP4) (also called centaurin alpha), identified as a brain-specific InsP4/PtdInsP3 (PIP3)-binding protein, has been shown to be localized in human brain, specifically expressed in neurons. Several casein kinases have been found to be involved in Alzheimer's disease (AD) pathology. Since casein kinase I was reported to possess a binding domain for p42(IP4), we here investigated the expression and localization of p42(IP4) in AD brains. In cortical neurons of AD brains intracellular immunostaining for p42(IP4) exceeded the level seen in these neurons of normal brain. Statistically, significantly more p42(IP4)-immunoreactive neurons were found in temporal and angular cortex of AD patients as compared to control brain. Mostly impressively, neuritic plaques displayed a very prominent signal. Thus, we suggest that the up-regulated p42(IP4) in AD neurons may serve as a docking protein to recruit signaling molecules such as different subtypes of casein kinase I to the plasma membrane. This is the first indication for a functional interaction of these protein in possible neuronal damage. Therefore proteins such as p42(IP4), central players in signaling, may be appropriate targets for preventing neurodegenerative processes.
Reiser
Georg
G
Klinik für Psychiatrie, Psychotherapie und Psychosomatische Medizin, Medizinische Fakultät, Leipziger Strasse 44, 39120 Magdeburg, Germany.
Bernstein
Hans-Gert
HG
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis*; D047388:Casein Kinases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D058225:Plaque, Amyloid / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*
C100956:ADAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C061107:inositol-1,3,4,5-tetrakisphosphate receptor; D011494:Protein Kinases; D047388:Casein Kinases