title: Calneurons provide a calcium threshold for trans-Golgi network to plasma membrane trafficking.
abstract: Phosphatidylinositol 4-OH kinase IIIbeta (PI-4Kbeta) 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-4Kbeta, 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-4Kbeta 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-4Kbeta activity and vesicle trafficking.
authors.affiliation: Project Group Neuroplasticity, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Mikhaylova
authors.forename: Pasham Parameshwar
authors.initials: PP
authors.lastname: Reddy
authors.forename: Thomas
authors.initials: T
authors.lastname: Munsch
authors.forename: Peter
authors.initials: P
authors.lastname: Landgraf
authors.forename: Shashi Kumar
authors.initials: SK
authors.lastname: Suman
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Smalla
authors.forename: Eckart D
authors.initials: ED
authors.lastname: Gundelfinger
authors.forename: Yogendra
authors.initials: Y
authors.lastname: Sharma
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kreutz
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D051580:Neuronal Calcium-Sensor Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C516555:calneuron I, rat; C516556:calneuron II, rat; C101464:frequenin calcium sensor proteins; D019870:1-Phosphatidylinositol 4-Kinase; D002118:Calcium