RRC ID 3612
Author Parker JA, Metzler M, Georgiou J, Mage M, Roder JC, Rose AM, Hayden MR, Néri C.
Title Huntingtin-interacting protein 1 influences worm and mouse presynaptic function and protects Caenorhabditis elegans neurons against mutant polyglutamine toxicity.
Journal J. Neurosci.
Abstract Huntingtin-interacting protein 1 (HIP1) was identified through its interaction with htt (huntingtin), the Huntington's disease (HD) protein. HIP1 is an endocytic protein that influences transport and function of AMPA and NMDA receptors in the brain. However, little is known about its contribution to neuronal dysfunction in HD. We report that the Caenorhabditis elegans HIP1 homolog hipr-1 modulates presynaptic activity and the abundance of synaptobrevin, a protein involved in synaptic vesicle fusion. Presynaptic function was also altered in hippocampal brain slices of HIP1-/- mice demonstrating delayed recovery from synaptic depression and a reduction in paired-pulse facilitation, a form of presynaptic plasticity. Interestingly, neuronal dysfunction in transgenic nematodes expressing mutant N-terminal huntingtin was specifically enhanced by hipr-1 loss of function. A similar effect was observed with several other mutant proteins that are expressed at the synapse and involved in endocytosis, such as unc-11/AP180, unc-26/synaptojanin, and unc-57/endophilin. Thus, HIP1 is involved in presynaptic nerve terminal activity and modulation of mutant polyglutamine-induced neuronal dysfunction. Moreover, synaptic proteins involved in endocytosis may protect neurons against amino acid homopolymer expansion.
Volume 27(41)
Pages 11056-64
Published 2007-10-10
DOI 10.1523/JNEUROSCI.1941-07.2007
PII 27/41/11056
PMID 17928447
PMC PMC6672856
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* DNA-Binding Proteins / genetics DNA-Binding Proteins / physiology* Excitatory Postsynaptic Potentials / drug effects Excitatory Postsynaptic Potentials / genetics Excitatory Postsynaptic Potentials / physiology Mice Mice, Knockout Mutation* Neurons / drug effects Neurons / physiology* Peptides / toxicity* Presynaptic Terminals / drug effects Presynaptic Terminals / pathology Presynaptic Terminals / physiology* Synapses / drug effects Synapses / genetics Synapses / physiology
IF 6.074
Times Cited 34
C.elegans tm2207