On the targeting of voltage-gated calcium channels to neurotransmitter release sites.

At the presynaptic active zone, voltage-gated Ca channels (Cas) mediate Ca entry for neurotransmitter release. Cas are a large family of proteins, and different subtypes have distinct localizations across neuronal somata, dendrites and axons. Here, we review how neurons establish and maintain a specific Ca repertoire at their active zones.

The intracellular C-terminus confers compartment-specific targeting of voltage-gated calcium channels.

To achieve the functional polarization that underlies brain computation, neurons sort protein material into distinct compartments. Ion channel composition, for example, differs between axons and dendrites, but the molecular determinants for their polarized trafficking remain obscure. Here, we identify mechanisms that target voltage-gated Ca channels (Cas) to distinct subcellular compartments.

The intracellular C-terminus confers compartment-specific targeting of voltage-gated Ca channels.

To achieve the functional polarization that underlies brain computation, neurons sort protein material into distinct compartments. Ion channel composition, for example, differs between axons and dendrites, but the molecular determinants for their polarized trafficking remain obscure. Here, we identify the mechanisms that target voltage-gated Ca channels (Cas) to distinct subcellular compartments.

FHL2 anchors mitochondria to actin and adapts mitochondrial dynamics to glucose supply.

Mitochondrial movement and distribution are fundamental to their function. Here we report a mechanism that regulates mitochondrial movement by anchoring mitochondria to the F-actin cytoskeleton. This mechanism is activated by an increase in glucose influx and the consequent O-GlcNAcylation of TRAK (Milton), a component of the mitochondrial motor-adaptor complex.

The potassium channel subunit Kβ1 serves as a major control point for synaptic facilitation.

Analysis of the presynaptic action potential's (AP) role in synaptic facilitation in hippocampal pyramidal neurons has been difficult due to size limitations of axons. We overcame these size barriers by combining high-resolution optical recordings of membrane potential, exocytosis, and Ca in cultured hippocampal neurons. These recordings revealed a critical and selective role for K1 channel inactivation in synaptic facilitation of excitatory hippocampal neurons.

Synaptic vesicles transiently dock to refill release sites.

Synaptic vesicles fuse with the plasma membrane to release neurotransmitter following an action potential, after which new vesicles must 'dock' to refill vacated release sites. To capture synaptic vesicle exocytosis at cultured mouse hippocampal synapses, we induced single action potentials by electrical field stimulation, then subjected neurons to high-pressure freezing to examine their morphology by electron microscopy. During synchronous release, multiple vesicles can fuse at a single active zone.

Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points.

Neurotransmitter release depends on voltage-gated Na channels (Nas) to propagate an action potential (AP) successfully from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na channels. Using optical recordings of Ca and membrane voltage, we demonstrate here that Na channel β2 subunits (Naβ2s) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female).