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Calneurons provide a calcium threshold for trans-Golgi network to plasma membrane trafficking
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Calneurons provide a calcium threshold for trans-Golgi network to plasma membrane trafficking
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Journal Article
Calneurons provide a calcium threshold for trans-Golgi network to plasma membrane trafficking
2009
Overview
Phosphatidylinositol 4-OH kinase IIIβ (PI-4Kβ) is involved in the regulated local synthesis of phospholipids that are crucial for trans-Golgi network (TGN)-to-plasma membrane trafficking. In this study, we show that the calcium sensor proteins calneuron-1 and calneuron-2 physically associate with PI-4Kβ, inhibit the enzyme profoundly at resting and low calcium levels, and negatively interfere with Golgi-to-plasma membrane trafficking. At high calcium levels this inhibition is released and PI-4Kβ is activated via a preferential association with neuronal calcium sensor-1 (NCS-1). In accord to its supposed function as a filter for subthreshold Golgi calcium transients, neuronal overexpression of calneuron-1 enlarges the size of the TGN caused by a build-up of vesicle proteins and reduces the number of axonal Piccolo-Bassoon transport vesicles, large dense core vesicles that carry a set of essential proteins for the formation of the presynaptic active zone during development. A corresponding protein knockdown has the opposite effect. The opposing roles of calneurons and NCS-1 provide a molecular switch to decode local calcium transients at the Golgi and impose a calcium threshold for PI-4Kβ activity and vesicle trafficking.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
1-Phosphatidylinositol 4-Kinase - antagonists & inhibitors
/ 1-Phosphatidylinositol 4-Kinase - metabolism
/ Animals
/ Axons
/ Calcium
/ Calcium-Binding Proteins - genetics
/ Calcium-Binding Proteins - metabolism
/ Enzymes
/ Kinases
/ Lipids
/ Neuronal Calcium-Sensor Proteins - metabolism
/ Neurons
/ Plasma
/ Proteins
/ Rats
/ Sensors
