Glycolipid Intermembrane Transfer Is Accelerated by HET-C2, a Filamentous Fungus Gene Product Involved in the Cell−Cell Incompatibility Response

• Published in: Biochemistry (Easton) Vol. 42; no. 2; pp. 535 - 542
• Main Authors: Mattjus, Peter, Turcq, Béatrice, Pike, Helen M, Molotkovsky, Julian G, Brown, Rhoderick E
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.01.2003
• Subjects: Ascomycota; Ascomycota - chemistry; Ascomycota - cytology; Ascomycota - genetics; Ascomycota - physiology; Biochemistry, Molecular Biology; Biological Transport; Carrier Proteins; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Communication; Cell Communication - physiology; Cell Death; Cell Death - physiology; Cell Division; Cell Division - physiology; Cell Membrane; Cell Membrane - chemistry; Cell Membrane - metabolism; Extracellular Space; Extracellular Space - chemistry; Extracellular Space - metabolism; Fungal Proteins; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; Glycosphingolipids; Glycosphingolipids - chemistry; Glycosphingolipids - metabolism; Isoelectric Focusing; Life Sciences; Microbiology and Parasitology; Mycology; Phosphorylcholine; Phosphorylcholine - chemistry; Phosphorylcholine - metabolism; Protoplasts; Protoplasts - chemistry; Protoplasts - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - chemistry; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - physiology; Spores, Fungal; Spores, Fungal - chemistry; Spores, Fungal - metabolism; Static Electricity
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi026896x

Among filamentous fungi capable of mycelial growth, het genes play crucial roles by regulating heterokaryon formation between different individuals. When fusion occurs between fungal mycelia that differ genetically at their het loci, the resulting heterokaryotic cells are quickly destroyed. It is unclear how het gene products of Podospora anserina trigger heterokaryon incompatibility. One unexplored possibility is that glycosphingolipids play a role because the het-c2 gene encodes a protein that displays 32% sequence identity and an additional 30% similarity to the mammalian glycolipid transfer protein. Here, P. anserina protoplasts containing wild-type het-c2 genes were shown to have greater glycosphingolipid transfer activity than protoplasts with disrupted het-c2 genes, a condition previously linked to altered cell compatibility following hyphal fusion. The observed glycolipid transfer activity could not be accounted for by nonspecific lipid transfer protein activity. Direct assessment showed that purified, recombinant HET-C2 accelerates the intermembrane transfer of glycolipid in vitro, but that the HET-C2 activity is mitigated much less by negatively charged membranes than the mammalian glycolipid transfer protein. The findings are discussed within the context of HET-C2 being a member of an emerging family of ancestral sphingolipid transfer proteins that play important roles in cell proliferation and accelerated death.