Ubiquitin C-terminal hydrolase is an immediate-early gene essential for long-term facilitation in Aplysia

Cell. 1997 Apr 4;89(1):115-26. doi: 10.1016/s0092-8674(00)80188-9.

Abstract

The switch from short-term to long-term facilitation of the synapses between sensory and motor neurons mediating gill and tail withdrawal reflexes in Aplysia requires CREB-mediated transcription and new protein synthesis. We isolated several downstream genes, one of which encodes a neuron-specific ubiquitin C-terminal hydrolase. This rapidly induced gene encodes an enzyme that associates with the proteasome and increases its proteolytic activity. This regulated proteolysis is essential for long-term facilitation. Inhibiting the expression or function of the hydrolase blocks induction of long-term but not short-term facilitation. We suggest that the enhanced proteasome activity increases degradation of substrates that normally inhibit long-term facilitation. Thus, through induction of the hydrolase and the resulting up-regulation of the ubiquitin pathway, learning recruits a regulated form of proteolysis that removes inhibitory constraints on long-term memory storage.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / pharmacology
  • Aplysia / physiology*
  • Base Sequence
  • Blotting, Northern
  • Cells, Cultured / drug effects
  • Cells, Cultured / enzymology
  • Cyclic AMP / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Ganglia, Invertebrate / cytology
  • Genes, Immediate-Early / physiology*
  • Long-Term Potentiation / genetics*
  • Memory / physiology
  • Microinjections
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology
  • Nerve Tissue Proteins / metabolism
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / enzymology
  • Oligonucleotides, Antisense / pharmacology
  • Proteins / metabolism
  • RNA, Messenger / analysis
  • Serotonin / pharmacology
  • Substrate Specificity
  • Thiolester Hydrolases / genetics*
  • Thiolester Hydrolases / immunology
  • Thiolester Hydrolases / metabolism
  • Ubiquitin Thiolesterase
  • Ubiquitins / metabolism

Substances

  • Antibodies
  • Nerve Tissue Proteins
  • Oligonucleotides, Antisense
  • Proteins
  • RNA, Messenger
  • Ubiquitins
  • Serotonin
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Thiolester Hydrolases
  • Ubiquitin Thiolesterase

Associated data

  • GENBANK/U90177