Suppression of guanylyl cyclase ( 1 subunit) expression impairs neurite outgrowth and synapse maturation in cultured cerebellar granule cells

• Published in: Cell death and differentiation Vol. 16; no. 9; pp. 1266 - 1278
• Main Authors: López-Jiménez, M E, Bartolomé-Martín, D, Sánchez-Prieto, J, Torres, M
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.09.2009
• Subjects: Animals; Apoptosis; Cell death; Cells, Cultured; Cerebellum - cytology; Cerebellum - enzymology; Dehydrogenases; Electron microscopes; Enzymes; Fluorescent Dyes - pharmacology; GAP-43 Protein - metabolism; Gene Knockdown Techniques; Guanylate Cyclase - genetics; Guanylate Cyclase - metabolism; Kinases; Nervous system; Neurites - physiology; Nitric oxide; Proteins; Pyridinium Compounds - pharmacology; Quaternary Ammonium Compounds - pharmacology; Rats; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; RNA, Small Interfering - metabolism; Soluble Guanylyl Cyclase; Synapses - physiology; Synapsins - metabolism; Madrid Spain; Spain
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2009.57

The increased expression of different soluble guanylyl cyclase (sGC) subunits during development is consistent with these proteins participating in the formation and establishment of interneuronal contacts. Functional sGC is generated by the dimerization of an alpha-subunit (sGCalpha1/2) with the beta1-subunit (sGCbeta1), and both depletion of the sGCbeta1 subunit and inhibiting sGC activity impair neurite outgrowth. Similarly, impairing sGC activity diminishes the amount of growth-associated protein (GAP-43) and synapsin I, two proteins that participate in axon elongation and synaptogenesis, suggesting a role for sGC in these processes. Indeed, fewer synapses form when sGC is inhibited, as witnessed by FM1-43 imaging and synapsin I immunostaining, and the majority of synapses that do form remain functionally immature. These findings highlight the importance of sGC in the regulation of neurite outgrowth and synapse formation, and in the functional maturation of cerebellar granule cells in vitro.