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Increased Expression of Gα q/11 and of Phospholipase‐Cβ1/4 in Differentiated Human NT2‐N Neurons
Author(s) -
Novak James E.,
Agranoff Bernard W.,
Fisher Stephen K.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0742322.x
Subject(s) - retinoic acid , phospholipase c , cellular differentiation , activator (genetics) , biology , microbiology and biotechnology , gq alpha subunit , inositol , signal transduction , biochemistry , g protein , receptor , gene
The CNS is enriched in phosphoinositide‐specific phospholipase C (PLC) and in the G proteins linked to its activation. Although the regional distributions of these signaling components within the brain have been determined, neither their cell type‐specific localizations (i.e., neuronal versus glial) nor the functional significance of their high expression has been definitively established. In this study, we have examined the expression of phosphoinositide signaling proteins in human NT2‐N cells, a well characterized model system for CNS neurons. Retinoic acid‐mediated differentiation of NT2 precursor cells to the neuronal phenotype resulted in five‐ to 15‐fold increases in the expression of PLC‐β1, PLC‐β4, and Gα q/11 (the prime G protein activator of these isozymes). In contrast, the expression of PLC‐β3 and PLC‐γ1 was markedly reduced following neuronal differentiation. Similar alterations in cell morphology and in the expression of PLC‐β1, PLC‐β3, and Gα q/11 expression were observed when NT2 cells were differentiated with berberine, a compound structurally unrelated to retinoic acid. NT2‐N neurons exhibited a significantly higher rate of phosphoinositide hydrolysis than NT2 precursor cells in response to direct activation of either G proteins or PLC. These results indicate that neuronal differentiation of NT2 cells is associated with dramatic changes in the expression of proteins of the phosphoinositide signaling system and that, accordingly, differentiated NT2‐N neurons possess an increased ability to hydrolyze inositol lipids.