Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs

Cell. 2002 Jan 11;108(1):121-33. doi: 10.1016/s0092-8674(01)00635-3.


Munc13-1 is a presynaptic protein with an essential role in synaptic vesicle priming. It contains a diacylglycerol (DAG)/beta phorbol ester binding C(1) domain and is a potential target of the DAG second messenger pathway that may act in parallel with PKCs. Using genetically modified mice that express a DAG/beta phorbol ester binding-deficient Munc13-1(H567K) variant instead of the wild-type protein, we determined the relative contribution of PKCs and Munc13-1 to DAG/beta phorbol ester-dependent regulation of neurotransmitter release. We show that Munc13s are the main presynaptic DAG/beta phorbol ester receptors in hippocampal neurons. Modulation of Munc13-1 activity by second messengers via the DAG/beta phorbol ester binding C(1) domain is essential for use-dependent alterations of synaptic efficacy and survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Cells, Cultured
  • Diglycerides / metabolism*
  • Gene Expression / physiology
  • Hippocampus / cytology
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology
  • Phorbol Esters / pharmacology*
  • Point Mutation / physiology
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Synapses / enzymology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Diglycerides
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Phorbol Esters
  • Unc13b protein, mouse
  • Protein Kinase C