Journal
MOLECULES AND CELLS
Volume 32, Issue 3, Pages 289-294Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
DOI: 10.1007/s10059-011-0075-x
Keywords
Alzheimer's disease; co-immunoprecipitation; GST pulldown; intracellular Ca2+ L-type Ca2+ channels
Categories
Funding
- Mid-Career Researcher Program [20110000094]
- Pioneer Grant [20110002117]
- BRC [2011K000272]
- Ministry of Education, Science and Technology, the Republic of Korea [2009-0076837]
- National Research Foundation of Korea [2009-0079000, 2009-0076837, 22-2009-00-006-00, 2011-0002117] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Overload of intracellular Ca2+ has been implicated in the pathogenesis of neuronal disorders, such as Alzheimer's disease. Various mechanisms produce abnormalities in intracellular Ca2+ homeostasis systems. L-type Ca2+ channels have been known to be closely involved in the mechanisms underlying the neurodegenerative properties of amyloid-beta (A beta) peptides. However, most studies of L-type Ca2+ channels in A beta-related mechanisms have been limited to Ca(V)1.2, and surprisingly little is known about the involvement of Ca(V)1.3 in A beta-induced neuronal toxicity. In the present study, we examined the expression patterns of Ca(V)1.3 after A beta(25-35) exposure for 24 h and compared them with the expression patterns of Ca(V)1.2. The expression levels of Ca(V)1.3 were not significantly changed by A beta(25-35) at both the mRNA levels and the total protein level in cultured hippocampal neurons. However, surface protein levels of Ca(V)1.3 were significantly increased by A beta(25-35), but not by A beta(35-25). We next found that acute treatment with A beta(25-35) increased Ca(V)1.3 channel activities in HEK293 cells using whole-cell patch-clamp recordings. Furthermore, using GTP pulldown and co-immunoprecipitation assays in HEK293 cell lysates, we found that amyloid precursor protein interacts with beta(3) subunits of Ca2+ channels instead of Ca(V)1.2 or Ca(V)1.3 alpha(1) subunits. These results show that A beta(25-35) chronically or acutely upregulates Ca(V)1.3 in the rat hippocampal and human kidney cells (HEK293). This suggests that Ca(V)1.3 has a potential role along with Ca(V)1.2 in the pathogenesis of Alzheimer's disease.
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