title: Dependence receptor involvement in subtilisin-induced long-term depression and in long-term potentiation.
abstract: The serine protease subtilisin induces a form of long-term depression (LTD) which is accompanied by a reduced expression of the axo-dendritic guidance molecule Unco-ordinated-5C (Unc-5C). One objective of the present work was to determine whether a loss of Unc-5C function contributed to subtilisin-induced LTD by using Unc-5C antibodies in combination with the pore-forming agents Triton X-100 (0.005%) or streptolysin O in rat hippocampal slices. In addition we have assessed the effect of subtilisin on the related dependence receptor Deleted in Colorectal Cancer (DCC) and used antibodies to this protein for functional studies. Field excitatory postsynaptic potentials (fEPSPs) were analyzed in rat hippocampal slices and protein extracts were used for Western blotting. Subtilisin produced a greater loss of DCC than of Unc-5C, but the antibodies had no effect on resting excitability or fEPSPs and did not modify subtilisin-induced LTD. However, antibodies to DCC but not Unc-5C did reduce the amplitude of theta-burst long-term potentiation (LTP). In addition, two inhibitors of endocytosis - dynasore and tat-gluR2(3Y) - were tested and, although the former compound had no effect on neurophysiological responses, tat-gluR2(3Y) did reduce the amplitude of subtilisin-induced LTD without affecting the expression of DCC or Unc-5C but with some loss of PostSynaptic Density Protein-95. The results support the view that the dependence receptor DCC may be involved in LTP and suggest that the endocytotic removal of a membrane protein or proteins may contribute to subtilisin-induced LTD, although it appears that neither Unc-5C nor DCC are involved in this process.
authors: Institute of Neurosciences and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. Electronic address: Trevor.Stone@glasgow.ac.uk.
authors: Trevor W
authors: TW
authors: Stone
authors: The Ashtead Hospital, The Warren, Ashtead, Surrey KT21 2SB, UK.
authors: L Gail
authors: LG
authors: Darlington
authors: Institute of Neurosciences and Psychology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
authors: Caroline M
authors: CM
authors: Forrest
mesh_terms: D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects*; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D020860:Subtilisin / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000502:physiology; D013995:Time
chemical_list: D020860:Subtilisin
keywords: DCC; Deleted in Colorectal Cancer; hippocampus; plasticity; serine proteases; subtilisin