The Polyketide MPBD Initiates the SDF-1 Signaling Cascade That Coordinates Terminal Differentiation in Dictyostelium

Abstract

Dictyostelium uses a wide array of chemical signals to coordinate differentiation as it switches from a unicellular to a multicellular organism. MPBD, the product of the polyketide synthase encoded by stlA, regulates stalk and spore differentiation by rapidly stimulating the release of the phosphopeptide SDF-1. By analyzing specific mutants affected in MPBD or SDF-1 production, we delineated a signal transduction cascade through the membrane receptor CrlA coupled to G␣1, leading to the inhibition of GskA so that the precursor of SDF-1 is released. It is then processed by the extracellular protease of TagB on prestalk cells. SDF-1 apparently acts through the adenylyl cyclase ACG to activate the cyclic AMP (cAMP)-dependent protein kinase A (PKA) and trigger the production of more SDF-1. This signaling cascade shows similarities to the SDF-2 signaling pathway, which acts later to induce rapid spore encapsulation.

Steely Enzymes Are Involved in Prestalk and Prespore Pattern Formation

“…SteelyA synthesizes 4-methyl-5-pentylbenzene-1,3-diol (MPBD), and the major defect of the stlA knockout mutants is aberrant spore maturation. 14,15) Whereas stlA null mutants show glassy sori, and most of the cells in the sori remain amoebae-like without cell walls, addition of MPBD to the culture agar restored functional spore maturation. 14) SteelyB produces the backbone of 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl) hexan-1-on (DIF-1), the (pre)stalkinducing factor.…”

The GATA transcription factor gene gtaG is required for terminal differentiation in Dictyostelium

“…The secreted peptides signals SDF-1 and SDF-2 are also components of the culmination-signaling pathway (Anjard et al, 1998a,b;Anjard et al, 2011;Anjard and Loomis, 2005). To study the GtaG pathway further, we tested the gtaG − cells in mixing experiments with tagB − cells, which cannot process the precursor of SDF-1, and acbA − cells, which cannot produce the precursor of SDF-2 (tagB and acbA expression are independent of GtaG) (Fig.…”

“…The role of prestalk cells in signaling to prespore cells during culmination is well documented, because inactivation of prestalk cell differentiation by various means results in complete loss of sporulation that can be reversed by mixing with wild-type cells (Harwood et al, 1993;Shaulsky et al, 1995). Signaling is effected through an intricate system that coordinates culmination and terminal differentiation, involving secretion of the polyketide 4-methyl-5-pentylbenzene-1,3 diol (MPBD) that is produced by StlA and the small peptide SDF-1 that is processed by TagB (Anjard et al, 2011;Narita et al, 2011). In addition, c-di-GMP is a stalk-inducing morphogen that is also essential for spore formation in a non-cell-autonomous way, although the direct function of c-di-GMP in sporulation is unclear (Chen and Schaap, 2012).…”

“…GtaG has a small effect on the expression of pkaC as well, but it is not the major regulator of this central gene. GtaG might partially regulate crlA, which is the membrane receptor of MPBD and is required to release SDF-1 (Anjard et al, 2011). However, the expression of stlA ( polyketide synthase for MPBD), stlB ( polyketide synthase to produce the backbone of DIF-1) and dmtA (methyltransferase to catalyze the last step in DIF-1 synthesis) is not affected by loss of gtaG function.…”

Effects of deletion of the receptor CrlA on Dictyostelium aggregation and MPBD-mediated responses are strain dependent and not evident in strain Ax2

“…In addition, MPBD induces spore maturation in fruiting bodies (Sato et al, 2013, Narita et al, 2014. Previous studies suggest that MPBD is a component of the SDF-1 (Spore Differentiation Factor-1) signalling cascade (Anjard et al, 2011). SDF-1 is a phospho-peptide, which induces spore encapsulation in sporogenous cells that overexpress PkaC.…”