Abstract
During normal development and response to environmental stress, fungi must coordinate synthesis of the cell wall and plasma membrane. Septins, small cytoskeletal GTPases, colocalize with sterol-rich regions in the membrane and facilitate recruitment of cell wall synthases during dynamic wall remodeling. In this study we show that null mutants of the core septins in Aspergillus nidulans, ΔaspAcdc11, ΔaspBcdc3, ΔaspCcdc12, and ΔaspDcdc10, are sensitive to cell wall-disturbing agents known to activate the cell wall integrity MAPK pathway and that this sensitivity can be remediated by osmotic support. Septin null mutants showed changes in cell wall polysaccharide composition and organization and in chitin synthase localization. Double mutant analysis suggested core septins function downstream of the final kinase of the cell wall integrity pathway. Null mutants of the core septins and of noncore septin AspE were resistant to ergosterol and sphingolipid biosynthesis-disrupting agents. Septins were mislocalized after treatment with sphingolipid biosynthesis-disrupting agents and, to a lesser extent, phosphoinositide biosynthesis- disrupting agents. When septin deletion mutants were challenged with both membrane-disturbing and cell wall-disturbing agents in combination, remediation of the membrane defect restored proper growth, but remediation of the cell wall defect did not. Our data suggest that septins are required for proper coordination of the cell wall integrity pathway and lipid metabolism and that this role requires sphingolipids.