tailieunhanh - Báo cáo khoa học: Non-enzymatic developmental functions of acetylcholinesterase – the question of redundancy

FungalPichia stipitisand bacterialAzotobacter vinelandiipossess an alter-native pathway of l-rhamnose metabolism, which is different from the known bacterial pathway. In a previous study (Watanabe S, Saimura M & Makino K (2008) Eukaryotic and bacterial gene clusters related to an alternative pathway of non-phosphorylated l-rhamnose metabolism. | ỊFEBS Journal Non-enzymatic developmental functions of acetylcholinesterase - the question of redundancy Glynis Johnson Chrisna Swart and Samuel W. Moore Divisions of Paediatric Surgery Molecular Biology and Human Genetics University of Stellenbosch Tygerberg South Africa Keywords acetylcholinesterase heparan sulfate laminin neuroligin perlecan Correspondence G. Johnson Divisions of Paediatric Surgery Molecular Biology and Human Genetics Faculty of Health Sciences University of Stellenbosch PO Box 19063 Tygerberg 7505 South Africa FaX 27 21 933 7999 Tel 27 21 938 9422 E-mail gjo@ Received 13 June 2008 revised 13 August 2008 accepted 14 August 2008 doi Despite in vitro demonstrations of non-enzymatic morphogenetic functions in acetylcholinesterase AChE the AChE knockout phenotype is milder than might be expected casting doubt upon the relevance of such functions in vivo. Functional redundancy is a possible explanation. Using in vitro findings that AChE is able to bind to laminin-111 together with detailed information about the interaction sites as well as an epitope analysis of adhesion-inhibiting anti-AChE mAbs we have used molecular docking and bioinformatics techniques to explore this idea investigating structurally similar molecules that have a comparable spatiotemporal expression pattern in the embryonic nervous system. On this basis molecules with which AChE could be redundant are the syndecans glypicans perlecan the receptor tyrosine kinase Mer and the low-density lipoprotein receptor. It is also highly likely that AChE may be redundant with the homologous neuroligins although there is no evidence that the latter are expressed before synaptogenesis. AChE was observed to dock with Gas6 the ligand for Mer as well as with apolipoprotein E3 but not apolipoprotein E4 both at the same site as the laminin interaction. These findings suggest that AChE may show direct functional redundancy with one or more of these molecules .