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Nitric oxide and cGMP signal transduction positively regulates the motility of human neuronal precursor (NT2) cells
Author(s) -
Tegenge Million Adane,
Bicker Gerd
Publication year - 2009
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 - 10.1111/j.1471-4159.2009.06279.x
Subject(s) - soluble guanylyl cyclase , microbiology and biotechnology , signal transduction , biology , motility , nitric oxide , retinoic acid , neurite , cellular differentiation , cell culture , cell growth , biochemistry , endocrinology , in vitro , guanylate cyclase , genetics , gene
Developmental studies in both vertebrates and invertebrates implicate an involvement of nitric oxide (NO) signaling in cell proliferation, neuronal motility, and synaptic maturation. However, it is unknown whether NO plays a role in the development of the human nervous system. We used a model of human neuronal precursor cells from a well‐characterized teratocarcinoma cell line (NT2). The precursor cells proliferate during retinoic acid treatment as spherical aggregate culture that stains for nestin and βIII‐tubulin. Cells migrate out of the aggregates to acquire fully differentiated neuronal phenotypes. The cells express neuronal nitric oxide synthase and soluble guanylyl cyclase (sGC), an enzyme that synthesizes cGMP upon activation by NO. The migration of the neuronal precursor cell is blocked by the use of nNOS, sGC, and protein kinase G (PKG) inhibitors. Inhibition of sGC can be rescued by a membrane permeable analog of cGMP. In gain of function experiments the application of a NO donor and cGMP analog facilitate cell migration. Our results from the differentiating NT2 model neurons point towards a vital role of the NO/cGMP/PKG signaling cascade as positive regulator of cell migration in the developing human brain.