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Participation of chaperones in the intracellular trafficking and functional expression of ASIC2 in glioma cells
Author(s) -
VilaCarriles Wanda Helena,
Fuller Catherine M.,
Benos Dale J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a536
Subject(s) - glioma , calnexin , calreticulin , amiloride , epithelial sodium channel , biology , intracellular , microbiology and biotechnology , chemistry , endoplasmic reticulum , cancer research , sodium , organic chemistry
Gliomas are primary brain tumors with a complex biology and a propensity for invasion into normal brain tissue. High‐grade glioma cells possess an amiloride sensitive current. This current is not seen in normal astrocytes or low‐grade tumor cells. Inhibition of this current decreases glioma growth and cell migration making it a potential therapeutic target. Our results suggest that the acid‐sensing ion channels (ASICs) and other members of the Epithelial Na+ Channel (ENaC)/Degenerin (Deg) family constitute this current pathway. We have shown that in glioma cells, ASIC2 is trapped in the ER and that loss of surface expression of this subunit is associated with appearance of the amiloride‐sensitive current (Vila‐Carriles et al., J. Biol. Chem . 28 :, 2006). We now show that two‐fold more of the ER chaperone, Hsc70, co‐immunoprecipitates with ASIC2 in glioma cells than in normal astrocytes. In contrast, there was no difference in the amount of three other chaperones (calnexin, calreticulin, and GRP78) that co‐immunoprecipitated with ASIC2 from glioma cells and normal astrocytes. These results support an association between Hsc70 and ASIC2 that may underlie the increase retention of this ENaC/Deg subunit in the ER of the glioma cell. Supported by NIH Grant DK07545 and CA101952.