Related Experiment Video
Updated: May 5, 2026
07:42
Dissection of Hippocampal Dentate Gyrus from Adult Mouse
Published on: November 17, 2009
84.6K
Memory and synaptic deficits in Hip14/DHHC17 knockout mice.
Austen J Milnerwood1, Matthew P Parsons, Fiona B Young
1Department of Psychiatry and Brain Research Centre, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Summary
Loss of huntingtin interacting protein 14 (Hip14) disrupts synaptic function and impairs memory. This highlights the critical role of specific palmitoyl acyltransferases (PATs) in maintaining cognitive health and suggests therapeutic targets for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Palmitoylation is a key post-translational modification regulating synaptic protein function.
- This process is rapid, reversible, and activity-dependent, crucial for synaptic plasticity.
- Huntingtin interacting protein 14 (Hip14/DHHC17) is a palmitoyl acyltransferase (PAT) involved in protein modification.
Purpose of the Study:
- To investigate the role of Hip14 in synaptic function and cognitive processes.
- To determine the impact of constitutive Hip14 loss on hippocampal memory and synaptic plasticity.
- To explore the significance of individual PATs in regulating physiology and cognition.
Main Methods:
- Constitutive knockout of Hip14 (DHHC17) in a model system.
- Electrophysiological recordings to assess synaptic function in various brain regions.
- Behavioral testing to evaluate hippocampal memory and synaptic plasticity.
Main Results:
- Constitutive loss of Hip14 leads to significant alterations in synaptic function across brain regions.
- Hip14 deficiency markedly impairs hippocampal memory and synaptic plasticity.
- Despite overlapping substrate pools among PATs, individual PAT function has profound physiological and cognitive effects.
Conclusions:
- Hip14 is essential for normal synaptic function, memory, and learning.
- Specific PATs play critical, non-redundant roles in synaptic modification and maintenance.
- Targeting PATs may offer a therapeutic strategy for cognitive deficits in neurodegenerative diseases.
