Role of protein S-acylation in branching of dendrites?

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Whereas palmitoylation of transmembrane proteins has been shown to initiate conformational changes, regulate membrane domain association or protein complex formation, alterations of cell morphology have not been established. We found that the palmitoylated TMD of a viral glycoprotein causes arborisation of the plasma membrane (PM) in cultured cells, and that specific inhibition of this lipidation largely abolishes this branching. Therefore, we hypothesize that palmitoylation of the TMD of specific transmembrane proteins is involved in membrane branching, e.g. dentrite formation. In this application we propose to identify eukaryotic transmembrane protein(s) that arborise membranes, using dentrites as a model. To this end we plan to analyse cell morphology after ectopic expression of a set of bioinformatically identified mammalian palmitoylable candidate proteins in cell culture, complemented by a neuronal cell-specific RNAi-screen in Drosophila. Resulting proteins will be validated by cell biological approaches and characterized biochemically. We intend to gain first insights into the mechanism underlying branching of membranes.