Saccharomyces cerevisiae Mid2p is a potential cell wall stress sensor and upstream activator of the PKC1-MPK1 cell integrity pathway

The MID2 gene of Saccharomyces cerevisiae encodes a protein with structural features indicative of a plasma membrane-associated cell wall sensor. MID2 was isolated as a multicopy activator of the Skn7p transcription factor. D eletion of MID2 causes resistance to calcofluor white, diminished productio n of stress-induced cell wall chitin under a variety of conditions, and cha nges in growth rate and viability in a number of different cell wall biosyn thesis mutants. Overexpression of MID2 causes hyperaccumulation of chitin a nd increased sensitivity to calcofluor white, alpha-Factor hypersensitivity of mid2 Delta mutants can be suppressed by overexpression of upstream elem ents of the cell integrity pathway, including PKC1, RHO1, WSC1, and WSC2. M id2p and Wsc1p appear to have overlapping roles in maintaining cell integri ty since mid2 Delta wsc1 Delta mutants are inviable on medium that does not contain osmotic support. A role for MID2 in the cell integrity pathway is further supported by the finding that MID2 is required for induction of Mpk 1p tyrosine phosphorylation during exposure to or-factor, calcofluor white, or high temperature. Our data are consistent with a role for Mid2p in sens ing cell wall stress and in activation of a response that includes both inc reased chitin synthesis and the Mpk1p mitogen-activated protein kinase cell integrity pathway. In addition, we have identified an open reading frame, MTL1, which encodes a protein with both structural and functional similarit y to Mid2p.