Pin1 and PKMzeta sequentially control dendritic protein synthesis
Pamela R Westmark1, Cara J Westmark, SuQing Wang
1Department of Pathology and Laboratory Medicine and Waisman Center for Developmental Disabilities, University of Wisconsin, Madison, WI 53705, USA.
Science Signaling
|March 11, 2010
Summary
Pin1 protein inhibits dendritic protein synthesis crucial for learning and memory. Its suppression enhances late long-term potentiation (LTP) by increasing protein translation in the brain.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Dendritic protein synthesis is essential for certain forms of learning and memory, including long-term potentiation (LTP).
- The regulation of protein synthesis in neuronal dendrites is a critical process for synaptic plasticity.
Purpose of the Study:
- To investigate the role of Pin1 (protein interacting with NIMA 1), a peptidyl-prolyl isomerase, in regulating dendritic translation.
- To elucidate the molecular mechanisms by which Pin1 affects protein synthesis and its impact on LTP.
Main Methods:
- Immunohistochemical analysis to detect Pin1 localization in dendritic spines and shafts.
- Biochemical assays to assess the effect of Pin1 suppression on protein synthesis.
- Electrophysiological recordings of LTP in hippocampal slices from wild-type and Pin1 knockout (Pin1-/-) mice.
- Western blot analysis to measure levels of PKCzeta and PKMzeta.
Main Results:
- Pin1 was found in dendritic spines and shafts and inhibits glutamatergic signaling-induced protein synthesis.
- Suppression of Pin1 led to increased dendritic translation, potentially involving eIF4E and 4E-BP1/2.
- Pin1-/- mice exhibited normal early LTP (E-LTP) but significantly enhanced late LTP (L-LTP).
- Increased levels of Protein Kinase C zeta (PKCzeta) and Protein Kinase M zeta (PKMzeta) were observed in Pin1-/- mouse brain, and PKMzeta activity was necessary for maintaining dendritic translation.
Conclusions:
- Glutamate-induced dendritic protein synthesis is sequentially regulated by Pin1 and PKMzeta signaling.
- PKMzeta interacts with and inhibits Pin1 through phosphorylation, suggesting a feedback mechanism.
- Pin1 plays a crucial inhibitory role in regulating protein synthesis required for the maintenance of late LTP.
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