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Lipid dynamics at dendritic spines.

Dotti CG, Esteban JA, Ledesma MD - Front Neuroanat (2014)

Bottom Line: However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants.Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling.We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

View Article: PubMed Central - PubMed

Affiliation: Centro Biología Molecular Severo Ochoa, CSIC-UAM Madrid, Spain.

ABSTRACT
Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

No MeSH data available.


Related in: MedlinePlus

PIP metabolism in spine plasticity. Activation of NMDARc modulate AMPARc trafficking through spatially and timely controlled activity of PIPs and their metabolic enzymes. On one hand, PI3K association with AMPARc is required for receptor cell surface delivery during LTP. On the other hand, PTEN activity leading to PIP3 downregulation promotes migration of AMPARc from the postsynaptic density to the perisynaptic membrane. This depresses AMPARc synaptic responses by promoting receptor endocytosis during LTD. Moreover, signaling pathways initiated by PIP3 or PIP2, in which Akt/mTOR, DAG and IP3 are involved, contribute to actin remodeling and spine changes in size.
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Figure 3: PIP metabolism in spine plasticity. Activation of NMDARc modulate AMPARc trafficking through spatially and timely controlled activity of PIPs and their metabolic enzymes. On one hand, PI3K association with AMPARc is required for receptor cell surface delivery during LTP. On the other hand, PTEN activity leading to PIP3 downregulation promotes migration of AMPARc from the postsynaptic density to the perisynaptic membrane. This depresses AMPARc synaptic responses by promoting receptor endocytosis during LTD. Moreover, signaling pathways initiated by PIP3 or PIP2, in which Akt/mTOR, DAG and IP3 are involved, contribute to actin remodeling and spine changes in size.

Mentions: Several enzymes tightly control PIP turnover at dendritic spines (Figure 3). Biochemical and imaging experiments demonstrated that the phosphatase and tensin homolog deleted on chromosome ten (PTEN), which converts PIP3 into PIP2 (Maehama and Dixon, 1999), is recruited to dendritic spines upon NMDARc but not AMPARc activation (Jurado et al., 2010). NMDARc activation triggers a biphasic regulation of PTEN mobility in dendritic spines. First, there is a rapid and transient increase in mobility independent from PTEN interactions through its PDZ motif. A longer-lasting and PDZ-dependent anchoring of PTEN to the postsynaptic density follows this phase. This regulated mechanism of recruitment of PTEN may provide means to achieve synapse-specific modulation of PIP3 signaling during plasticity. The enhancement of PTEN lipid phosphatase activity is able to drive depression of AMPARc-mediated synaptic responses (Jurado et al., 2010). Consistently, mice with altered PTEN expression show multiple impairments in synaptic function including LTP and LTD (Wang et al., 2006; Fraser et al., 2008).


Lipid dynamics at dendritic spines.

Dotti CG, Esteban JA, Ledesma MD - Front Neuroanat (2014)

PIP metabolism in spine plasticity. Activation of NMDARc modulate AMPARc trafficking through spatially and timely controlled activity of PIPs and their metabolic enzymes. On one hand, PI3K association with AMPARc is required for receptor cell surface delivery during LTP. On the other hand, PTEN activity leading to PIP3 downregulation promotes migration of AMPARc from the postsynaptic density to the perisynaptic membrane. This depresses AMPARc synaptic responses by promoting receptor endocytosis during LTD. Moreover, signaling pathways initiated by PIP3 or PIP2, in which Akt/mTOR, DAG and IP3 are involved, contribute to actin remodeling and spine changes in size.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126552&req=5

Figure 3: PIP metabolism in spine plasticity. Activation of NMDARc modulate AMPARc trafficking through spatially and timely controlled activity of PIPs and their metabolic enzymes. On one hand, PI3K association with AMPARc is required for receptor cell surface delivery during LTP. On the other hand, PTEN activity leading to PIP3 downregulation promotes migration of AMPARc from the postsynaptic density to the perisynaptic membrane. This depresses AMPARc synaptic responses by promoting receptor endocytosis during LTD. Moreover, signaling pathways initiated by PIP3 or PIP2, in which Akt/mTOR, DAG and IP3 are involved, contribute to actin remodeling and spine changes in size.
Mentions: Several enzymes tightly control PIP turnover at dendritic spines (Figure 3). Biochemical and imaging experiments demonstrated that the phosphatase and tensin homolog deleted on chromosome ten (PTEN), which converts PIP3 into PIP2 (Maehama and Dixon, 1999), is recruited to dendritic spines upon NMDARc but not AMPARc activation (Jurado et al., 2010). NMDARc activation triggers a biphasic regulation of PTEN mobility in dendritic spines. First, there is a rapid and transient increase in mobility independent from PTEN interactions through its PDZ motif. A longer-lasting and PDZ-dependent anchoring of PTEN to the postsynaptic density follows this phase. This regulated mechanism of recruitment of PTEN may provide means to achieve synapse-specific modulation of PIP3 signaling during plasticity. The enhancement of PTEN lipid phosphatase activity is able to drive depression of AMPARc-mediated synaptic responses (Jurado et al., 2010). Consistently, mice with altered PTEN expression show multiple impairments in synaptic function including LTP and LTD (Wang et al., 2006; Fraser et al., 2008).

Bottom Line: However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants.Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling.We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

View Article: PubMed Central - PubMed

Affiliation: Centro Biología Molecular Severo Ochoa, CSIC-UAM Madrid, Spain.

ABSTRACT
Dynamic changes in the structure and composition of the membrane protrusions forming dendritic spines underlie memory and learning processes. In recent years a great effort has been made to characterize in detail the protein machinery that controls spine plasticity. However, we know much less about the involvement of lipids, despite being major membrane components and structure determinants. Moreover, protein complexes that regulate spine plasticity depend on specific interactions with membrane lipids for proper function and accurate intracellular signaling. In this review we gather information available on the lipid composition at dendritic spine membranes and on its dynamics. We pay particular attention to the influence that spine lipid dynamism has on glutamate receptors, which are key regulators of synaptic plasticity.

No MeSH data available.


Related in: MedlinePlus