Regulation of gene expression by pH of the growth medium in Aspergillus nidulans

Abstract

In the fungus Aspergillus nidulans the levels of a number of enzymes whose location is at least in part extracellular (e.g. acid phosphatase, alkaline phosphatase, phosphodiesterase) and of certain permeases (e.g. that for gamma-amino-n-butyrate) are controlled by the pH of the growth medium. For example, at acidic pH, levels of acid phosphatase are high and those of alkaline phosphatase are low whereas at alkaline pH the reverse is true. Mutations in five genes, palA, B, C, E and F, mimic the effects of growth at acid pH whereas mutations in pacC mimic the effects of growth at alkaline pH. palA, B, C, E and F mutations result in an intracellular pH (pHin) which is more alkaline than that of the wild type whereas pacC mutations result in a pHin more acidic than that of the wild type. This indicates that these mutations exert their primary effects on the regulation of gene expression by pH rather than on the pH homeostatic mechanism but that the expression of at least some component(s) of the pH homeostatic mechanism is subject to the pH regulatory system. It is suggested that pacC might be a wide domain regulatory gene whose product acts positively in some cases (e.g. acid phosphatase) and negatively in others (e.g. alkaline phosphatase). The products of palA, B, C, E and F are proposed to be involved in a metabolic pathway leading to synthesis of an effector molecule able to prevent the (positive and negative) action of the pacC product.(ABSTRACT TRUNCATED AT 250 WORDS)

The dermatophyte Trichophyton rubrum secretes an EDTA-sensitive alkaline phosphatase on high-phosphate medium

“…The regulation of this adaptive response has proved to be highly complex, not only because of the identification of a large number of genes involved in the signaling of Pi starvation, but also because the synthesis and secretion of these enzymes are under the action of nitrogen, carbon and pH regulatory circuits (8,13,19). The pH regulatory mechanism ensures that extracellular enzymes are secreted only at pH values at which they can function effectively.…”

“…For example, the use of nucleic acids as sources of inorganic phosphate (Pi) is based on the induction of structural proteins, permeases, and enzymes of the cell wall, in addition to the secretion of a variety of proteins and hydrolytic enzymes such as nucleases and acid and alkaline phosphatases in response to both Pi starvation and environmental pH signaling. This metabolic machinery permits the fungi, and other microorganisms, to use these macromolecules as sources of essential nutrients within a broad ambient pH range (8,11,17,19). Thus, it is also important to understand the metabolic responses that govern homeostatic pH and extracellular pH sensing in dermatophytes, since the pathogenicity of many microorganisms has been demonstrated to depend on the sensing of ambient pH in the host and on the ability to adapt, which involves installation, development, and survival in the host.…”

Characterization of the pH signal transduction pathway gene palA of Aspergillus nidulans and identification of possible homologs

“…pH regulation of gene expression is mediated by the zinc finger transcription factor PacC, whose 73-kDa full-length translation product is proteolyzed to yield a 29-kDa N-terminal fragment able to activate transcription of genes expressed at alkaline pH and prevent transcription of genes expressed at acid pH (15,17,19). The products of six genes, palA, -B, -C, -F, -H, and -I, form a signal transduction pathway through which alkaline ambient pH is able to elicit the conversion of the full-length form of PacC to the functional proteolyzed form (1,3,5,15,19). Loss-of-function mutations in these pal genes prevent this proteolytic conversion and mimic the effects of growth at acidic pH (1,3,5,7,15,18).…”

“…The products of six genes, palA, -B, -C, -F, -H, and -I, form a signal transduction pathway through which alkaline ambient pH is able to elicit the conversion of the full-length form of PacC to the functional proteolyzed form (1,3,5,15,19). Loss-of-function mutations in these pal genes prevent this proteolytic conversion and mimic the effects of growth at acidic pH (1,3,5,7,15,18).The mechanism of ambient pH signal transduction is an intriguing subject of scientific and biotechnological importance. We have previously shown that the palB gene product is likely to be a cysteine protease of the calpain family, albeit not the protease responsible for the final conversion of PacC to its functional form (5).…”

“…For example, acid phosphatase and the acid-pH-optimum ␥-aminobutyrate permease are synthesized preferentially in acidic media, whereas alkaline phosphatase and penicillin are synthesized preferentially in alkaline media (3,7,18). pH regulation of gene expression is mediated by the zinc finger transcription factor PacC, whose 73-kDa full-length translation product is proteolyzed to yield a 29-kDa N-terminal fragment able to activate transcription of genes expressed at alkaline pH and prevent transcription of genes expressed at acid pH (15,17,19).…”