negative regulation of L-glutamate import across plasma membrane

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of L-glutamate import into a cell. [GOC:TermGenie]

Negative regulation of L-glutamate import across the plasma membrane is a crucial process in maintaining neuronal homeostasis and preventing excitotoxicity. Glutamate, the primary excitatory neurotransmitter in the brain, is constantly being transported across the plasma membrane of neurons. Excessive glutamate accumulation in the synaptic cleft can lead to overstimulation of glutamate receptors and neuronal damage. This process involves a complex interplay of various mechanisms, including:

1. **Regulation of Glutamate Transporter Activity:** Glutamate transporters, primarily the excitatory amino acid transporter (EAAT) family, are responsible for removing glutamate from the synapse. These transporters are regulated by a multitude of factors, including:
* **Phosphorylation:** Phosphorylation of glutamate transporters by kinases, such as protein kinase C (PKC) and Ca2+/calmodulin-dependent protein kinase II (CaMKII), can alter their activity.
* **Intracellular Glutamate Levels:** High intracellular glutamate levels can inhibit transporter activity through feedback mechanisms.
* **Extracellular Calcium Levels:** Increased extracellular calcium concentrations can stimulate glutamate transporter activity.

2. **Presynaptic Inhibition:** The release of glutamate from presynaptic terminals can be regulated by various mechanisms, including:
* **Autoreceptor Activation:** Glutamate autoreceptors, such as metabotropic glutamate receptors (mGluRs), can inhibit glutamate release when activated.
* **Synaptic Plasticity:** Long-term depression (LTD) can decrease the release of glutamate by reducing the number of glutamate vesicles available for release.

3. **Glial Cell Involvement:** Astrocytes, the most abundant glial cells in the brain, play a crucial role in regulating glutamate homeostasis:
* **Glutamate Uptake:** Astrocytes express high levels of glutamate transporters (EAAT1 and EAAT2) that efficiently remove glutamate from the synaptic cleft.
* **Glutamine Synthesis:** Astrocytes convert glutamate to glutamine, which is then transported back to neurons for glutamate synthesis.

4. **Postsynaptic Regulation:** Postsynaptic neurons also contribute to negative regulation of glutamate import:
* **Desensitization of Glutamate Receptors:** Excessive glutamate stimulation can lead to desensitization of glutamate receptors, reducing their responsiveness to glutamate.
* **Glutamate Receptor Internalization:** Following prolonged glutamate exposure, glutamate receptors can be internalized from the cell surface, further decreasing glutamate signaling.

In summary, negative regulation of L-glutamate import across the plasma membrane is a multifaceted process involving a complex interplay of presynaptic, postsynaptic, and glial mechanisms. These mechanisms ensure that glutamate levels are tightly controlled, preventing excitotoxicity and maintaining neuronal function.'
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Proteins (1)

Compounds (18)