The Neuronal Cytoskeleton Controls Synaptic Transmission
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Material below summarizes the article MAP1B Light Chain Modulates Synaptic Transmission via AMPA Receptor Intracellular Trapping, published on September 13, 2017, in JNeurosci and authored by Rocío Palenzuela, Yolanda Gutiérrez, Jonathan E. Draffin, Argentina Lario, Marion Benoist, and José A. Esteban.
The regulation of neuronal communication in the brain is crucial for all our cognitive functions.
Traditionally, this has been thought to occur at the level of synaptic connections, where the neurotransmitter signal released from one neuron is received by the adjacent neuron via neurotransmitter receptors.
It is now well established that neurons can modify the number of neurotransmitter receptors present at the synapse. This process, a form of synaptic plasticity, is one basis for learning and memory.
What we have found now is that the neuron’s cytoskeleton, the scaffolding structure that gives shape to the neuron, can act as a remote control for synaptic strength by determining the number of neurotransmitter receptors that reach the synapse.
In neurons, as in most cells, the cytoskeleton is composed of a tubular network mostly made of polymers of tubulin. These structures, known as microtubules, are then used as a scaffold by myriad other proteins that use it for transport purposes, anchoring, or different types of regulation.
One of these proteins is microtubule-associated protein 1B (MAP1B), a fairly large molecule that is cleaved within the cell into a heavy chain and a light chain. The two chains associate to form a complex on microtubules. The complex is known to stabilize microtubules, but whether it has other functions in neurons is less clear. It is also unclear whether the chains always act in concert or display specific functions.
In this work, we showed that the light chain of MAP1B displays an asymmetric distribution within neurons and is more concentrated in the cytoskeleton of the dendrites.
This is quite intriguing because most neurotransmitter receptors are synthesized in the cell body and need to traffic along the microtubules of the dendrites on their way to the synapse. Interestingly, we found that MAP1B light chain forms an immobile scaffold on these microtubules, which interferes with the trafficking of cargo along dendrites.
We used confocal microscopy on living neurons to track a fluorescent version of neurotransmitter receptors of the AMPA-type (AMPA-type glutamate receptors).
We found that MAP1B light chain restricts the mobility of AMPA receptors along dendrites and impairs their access to the synaptic terminal. These microscopy observations were corroborated by electrophysiological recordings from these neurons, which revealed that overexpression of MAP1B light chain reduces synaptic strength.
What is the molecular mechanism linking MAP1B and AMPA receptors? Using different mutants of MAP1B, we found that GRIP1 (Glutamate Receptor Interacting Protein 1) is such a link.
As its name indicates, GRIP1 interacts with AMPA receptors, and it is also able to bind MAP1B. Using electrophysiological recordings and live imaging, we concluded that MAP1B light chain traps GRIP1-AMPA receptor complexes in the dendrite, and in this manner it controls AMPA receptor movement along the cytoskeleton.
Our work widens the current perspective on the biological role of cytoskeletal proteins in neurons. We now conclude that the cytoskeleton can influence synaptic transmission by gating the access of neurotransmitter receptors to the synapse.
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MAP1B Light Chain Modulates Synaptic Transmission via AMPA Receptor Intracellular Trapping. Rocío Palenzuela, Yolanda Gutiérrez, Jonathan E. Draffin, Argentina Lario, Marion Benoist, and José A. Esteban. JNeurosci Sep 2017, 0505-17; DOI: https://doi.org/10.1523/JNEUROSCI.0505-17.2017