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

Peter J M van Haastert*, Ineke Keizer-Gunnink, Henderikus Pots, Claudia Ortiz-Mateos, Douwe Veltman, Wouter van Egmond, Arjan Kortholt*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

5 Citaten (Scopus)
117 Downloads (Pure)

Samenvatting

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 Here we combine published experiments with many unpublished experiments performed in the past 45 years on the regulation and function of the cGMP signaling pathway.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 Gαβγ and monomeric Ras proteins. A fraction of the soluble guanylyl cyclase sGC binds with high affinity to a limited number of membrane binding site, which is essential for sGC to become activated by Ras and Gα 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.

Originele taal-2English
ArtikelnummermbcE21040171
Pagina's (van-tot)1-14
Aantal pagina's14
TijdschriftMolecular Biology of the Cell
Volume32
Nummer van het tijdschrift20
Vroegere onlinedatum4-aug.-2021
DOI's
StatusPublished - okt.-2021

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