Mutation in a Calpain-like Protease Affects the Posttranslational Mannosylation of Phosphatases in Aspergillus nidulans

Sérgio R. Nozawa , Gregory S. May , Monica S. Ferreira-Nozawa , Nilce M. Martinez-Rossi and Antonio Rossi.

Abstract: 

The ambient pH responses are mediated in A. nidulans by a conserved signal transduction pathway comprising at least seven genes (pacC and palA, etc) that have been cloned and sequenced. The palB gene codes for a calpain-like protease that is not involved directly in PacC processing, and the other pal genes have revealed only few functional features. In this communication, we show that the palB7 mutation drastically reduced the mannose and N-acetylgalactosamine content of the pacA-encoded acid phosphatase secreted by A. nidulans at pH 5.0, compared to a control strain. By using mRNA differential display reverse transcription and polymerase chain reaction, we isolated two cDNAs from the control strain (pabaA1) that were not detected in the palB7mutant strain and that encode a mannosyl transferase and a NADH-ubiquinone oxidoreductase. Thus, a defect in the posttranslational mannosylation of proteins could be the consequence of mutations in the palB gene, which codes for a nuclear calpain-like protease that may have specific functions in the processing of transcription factor(s) like its homologue, RIM13, in S. cereviseae. Further evidence in this direction comes from the demonstration that mutations in the mammalian calpain 3 protease rather than a structural defect can cause limb-girdle muscular dystrophy type 2A, and that these mutations are pathogenic only in a specific mitochondrial context (Richard et al., Cell, 81, 27-40, 1995). Thus, a defect in the posttranslational mannosylation of proteins could be the consequence of mutations in the proteolytic enzyme calpain 3 and could promote muscular dystrophy type 2A in humans. Financial support: FAPESP, CNPq, CAPES, FAEPA and Reitoria-USP.
2003

abstract No: 

Fungal Genet. Newsl. 50 (Supl):abstract

Full conference title: 

22nd Fungal Genetics Conference
    • Fungal Genetics Conference 22nd (2001)