Membrane topology of peripheral myelin protein 22

Peripheral myelin protein 22 (PMP22) is a structural component of compact p eripheral nerve myelin and is likely to play a role in the modulation of ce ll proliferation and cell spreading. Molecular genetics revealed that mutat ions affecting the PMP22 gene are responsible for the most common forms of hereditary motor and sensory neuropathies in humans. Computer analysis pred icts a tetraspan-membrane structure for the PMP22 protein. We have assessed the topology of PMP22 experimentally using chimeric proteins consisting of different PMP22 domains fused to reporter genes and internally tagged mole cules. Based on in vitro transcription/translation assays and immunohistoch emical analysis of transfected cells, we propose that PMP22 can adopt a non -tetraspan topology that has functional implications in normal and disease processes. (C) 2000 Wiley-Liss, Inc.