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Forty-five years of cGMP research in Dictyostelium: understanding the regulation and function of the cGMP pathway for cell movement and chemotaxis

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dc.creator Kortholt, Arjan
dc.creator van Haastert, Peter J. M.
dc.creator Keizer-Gunnink, Ineke
dc.creator Pots, Henderikus
dc.creator Ortiz-Mateos, Claudia
dc.creator Veltman, Douwe
dc.creator van Egmond, Wouter
dc.date 2021-10-01T00:00:00Z
dc.date.accessioned 2023-01-09T11:58:27Z
dc.date.available 2023-01-09T11:58:27Z
dc.identifier 0f389baf-ce17-43c1-abf6-2df34974bb02
dc.identifier 10.1091/mbc.e21-04-0171
dc.identifier https://avesis.sdu.edu.tr/publication/details/0f389baf-ce17-43c1-abf6-2df34974bb02/oai
dc.identifier.uri http://acikerisim.sdu.edu.tr/xmlui/handle/123456789/97560
dc.description In Dictyostelium, chemoattractants induce a fast cGMP response that mediates myosin filament formation in the rear of the cell. The major cGMP signaling pathway consists of a soluble guanylyl cyclase sGC, a cGMP-stimulated cGMP-specific phosphodiesterase, and the cGMP-target protein GbpC. Here we combine published experiments with many unpublished experiments performed in the past 45 years on the regulation and function of the cGMP signaling pathway. The chemoattractants stimulate heterotrimeric G alpha beta gamma and monomeric Ras proteins. A fraction of the soluble guanylyl cyclase sGC binds with high affinity to a limited number of membrane binding sites, which is essential for sGC to become activated by Ras and G alpha proteins. sGC can also bind to F-actin; binding to branched F-actin in pseudopods enhances basal sGC activity, whereas binding to parallel F-actin in the cortex reduces sGC activity. The cGMP pathway mediates cell polarity by inhibiting the rear: in unstimulated cells by sGC activity in the branched F-actin of pseudopods, in a shallow gradient by stimulated cGMP formation in pseudopods at the leading edge, and during cAMP oscillation to erase the previous polarity and establish a new polarity axis that aligns with the direction of the passing cAMP wave.
dc.language eng
dc.rights info:eu-repo/semantics/openAccess
dc.title Forty-five years of cGMP research in Dictyostelium: understanding the regulation and function of the cGMP pathway for cell movement and chemotaxis
dc.type info:eu-repo/semantics/article


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