Dependence receptor involvement in subtilisin-induced long-term depression and in long-term potentiation. (12th November 2016)

• Record Type: Journal Article
• Authors: Stone, Trevor W.; Darlington, L. Gail; Forrest, Caroline M.
• Is Part Of: Neuroscience. Volume 336(2016)
• Page Start: 49
• Page End: 62
• Publication Date: 2016-11-12
• Subjects: aCSF artificial cerebrospinal fluid -- CED Cambridge Electronic Design -- CNS central nervous system -- DCC Deleted in Colorectal Cancer -- fEPSPs field excitatory postsynaptic potentials -- HRP horse radish peroxidase -- LTD long-term depression -- LTP long-term potentiation -- NMDA N-methyl-d-aspartate -- Shh sonic hedgehog -- tPA tissue plasminogen activator -- Unc-5C Unco-ordinated-5C; Deleted in Colorectal Cancer -- DCC -- plasticity -- hippocampus -- subtilisin -- serine proteases; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.08.043
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: The serine protease subtilisin induces long-term depression (LTD) in rat hippocampus. Subtilisin also produced a loss of DCC and Unc-5C expression. An inhibitor of endocytosis – tat-gluR2(3Y) – reduced subtilisin-induced LTD. Antibodies to DCC but not Unc-5C reduced theta-burst LTP. DCC may be involved in LTP but not LTD. 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.