These proteins mediate cell–cell adhesion and are essential for morphogenesis beyond the loose aggregate stage and subsequent development and differentiation ( Benabentos et al., 2009 Dynes et al., 1994 Kibler et al., 2003). During streaming and loose-aggregate formation, the cells begin to express the tgrB1 and tgrC1 genes that encode two transmembrane proteins ( Benabentos et al., 2009). Later, the cells form loose aggregates that rotate around themselves while beginning to express cell-type-specific genes and acquiring tissue properties ( Kessin, 2001). Aggregation leads to streaming, in which polarized cells follow each other in a head-to-tail orientation using localized cAMP signals to coordinate motility ( Kessin, 2001 Kriebel et al., 2003 Ross and Newell, 1981). discoideum cells aggregate into mounds of ∼50,000 cells, using extracellular cAMP as a chemoattractant ( Artemenko et al., 2014). discoideum development, with a notable exception, which is the process of tissue formation and allorecognition that follows aggregation. It is broadly accepted that cAMP signaling participates in almost every step in D. discoideum development involves a complex interplay between the three adenylate cyclase genes and their relationships with PKA-C and cAMP signaling.ĬAMP waves propagate in exquisite patterns through the developing structures, starting at aggregation and continuing during slug migration and fruiting body formation ( Singer et al., 2019). Addition of extracellular cAMP or ectopic expression of acgA in acaA − cells restores aggregation and subsequent development ( Pitt et al., 1993, 1992), and ectopic expression of acaA in acrA − cells restores post-aggregative development ( Anjard et al., 2001). Moreover, the combined activities of acrA and acgA are required for prespore differentiation ( Alvarez-Curto et al., 2007). The third adenylate cyclase gene, acgA, is expressed in prespore cells during terminal differentiation and is essential for spore dormancy under high osmolarity ( van Es et al., 1996). Moreover, cAMP signaling regulates developmental gene expression, but different combinations of acaA and acrA mutations indicate that intracellular and extracellular cAMP signaling regulate gene expression in different ways ( Iranfar et al., 2003). Therefore, cAMP has an uncharacterized role in terminal differentiation in addition to activation of PKA-C. Overexpression of PKA-C suppresses the aggregationless phenotype and partially restores development, but not fruiting body formation or spore development ( Anjard et al., 2001).
Deletion of both acaA and acrA results in an aggregationless phenotype and absence of subsequent development. The second gene, acrA, is dispensable for aggregation but required for terminal differentiation ( Kim et al., 1998 Soderbom et al., 1999). Overexpression of the cAMP-dependent protein kinase catalytic subunit (PKA-C) in acaA − cells suppresses the aggregationless phenotype, leading to development with near-normal morphology and expression of developmental markers ( Wang and Kuspa, 1997). Deletion of acaA, which encodes the aggregation-stage enzyme, results in the absence of aggregation and subsequent development. discoideum genome harbors three adenylate cyclase genes that encode structurally different enzymes, which are dispensable for growth but required at different developmental stages ( Pitt et al., 1992 Soderbom et al., 1999 van Es et al., 1996). Therefore, TgrB1-TgrC1 signaling controls allorecognition and tissue formation, while cAMP is dispensable as long as PKA-C is overexpressed.Ĭyclic adenosine monophosphate (cAMP) is a key regulator of Dictyostelium discoideum development ( Loomis, 2014). The cells exhibited cell polarization, tissue formation and cooperation with allotype-compatible wild-type cells, but not with incompatible cells. We eliminated cAMP production by deleting the three adenylate cyclases and overexpressed PKA-C to enable aggregation. Here, we show that allorecognition and tissue formation do not require cAMP production as long as PKA is active. Previous studies have suggested that cAMP signaling might be dispensable for allorecognition and tissue formation, while others have argued that it is essential throughout development. The three adenylate cyclase genes, acaA, acrA and acgA are required for aggregation, culmination and spore dormancy, respectively, and some of their functions can be suppressed by activation of the cAMP-dependent protein kinase PKA. Extracellular and intracellular cAMP signaling are essential to many developmental processes. Allorecognition and tissue formation are interconnected processes that require signaling between matching pairs of the polymorphic transmembrane proteins TgrB1 and TgrC1 in Dictyostelium.
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