Dependence receptor involvement in subtilisin-induced long-term depression and in long-term potentiation

Stone, T. W. , Darlington, L. G. and Forrest, C. M. (2016) Dependence receptor involvement in subtilisin-induced long-term depression and in long-term potentiation. Neuroscience, 336, pp. 49-62. (doi: 10.1016/j.neuroscience.2016.08.043)

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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 analysed 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. (220).

Item Type:Articles
Additional Information:We gratefully acknowledge the financial support from Epsom Medical Research (reference TWS0012).
Glasgow Author(s) Enlighten ID:Forrest, Dr Caroline and Stone, Professor Trevor
Authors: Stone, T. W., Darlington, L. G., and Forrest, C. M.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Neuroscience
ISSN (Online):1873-7544
Published Online:31 August 2016
Copyright Holders:Copyright © 2016 Elsevier Ltd.
First Published:First published in Neuroscience 336:49-62
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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