Neuronal differentiation of NG108-15 cells has impact on nitric oxide- and membrane (natriuretic peptide receptor-A) cyclic GMP-generating proteins.
Cyclic GMP (cGMP), produced in response to either nitric oxide (NO) or certain peptides, controls important neuronal functions. NG108-15 cells were used to characterize the expression of NO- and cGMP-generating proteins and to identify potential alterations associated with neuronal differentiation (neurite outgrowth). We find that these cells contain exclusively neuronal NO synthase (nNOS) isoforms as well as both NO- (soluble guanylyl cyclase, sGC) and natriuretic peptide- (natriuretic peptide receptor-A, NPR-A) responsive cGMP-producing enzymes. The sGC beta(1) subunit (unlike protein phosphatase 2A subunits) is highly membrane-associated. Membrane concentrations of NPR-A and nNOS, but not sGC beta(1) protein are up-regulated with neuronal differentiation. Intriguingly, the rate of hormone-induced cGMP production by NPR-A is significantly diminished in differentiated cells. These findings support roles for NPR-A, the common receptor of atrial (ANP) and B-type (BNP) natriuretic peptide in mature neurons and provide evidence for pronounced changes in neuronal submembrane cGMP signalling during neuronal differentiation.
Müller
Dieter
D
Institute of Anatomy and Cell Biology, Justus-Liebig-University, 35385 Giessen, Germany. hans-dieter.mueller@anatomie.med.uni-giessen.de
Greenland
Karen J
KJ
Speth
Robert C
RC
Middendorff
Ralf
R
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism*; D006152:Cyclic GMP / Q000096:biosynthesis*; D006162:Guanylate Cyclase / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D000071756:Soluble Guanylyl Cyclase; D015854:Up-Regulation
D015415:Biomarkers; D021122:Protein Subunits; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D054648:Protein Phosphatase 2; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; D000071756:Soluble Guanylyl Cyclase; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP