title: Synaptic control of secretory trafficking in dendrites.
abstract: Localized signaling in neuronal dendrites requires tight spatial control of membrane composition. Upon initial synthesis, nascent secretory cargo in dendrites exits the endoplasmic reticulum (ER) from local zones of ER complexity that are spatially coupled to post-ER compartments. Although newly synthesized membrane proteins can be processed locally, the mechanisms that control the spatial range of secretory cargo transport in dendritic segments are unknown. Here, we monitored the dynamics of nascent membrane proteins in dendritic post-ER compartments under regimes of low or increased neuronal activity. In response to activity blockade, post-ER carriers are highly mobile and are transported over long distances. Conversely, increasing synaptic activity dramatically restricts the spatial scale of post-ER trafficking along dendrites. This activity-induced confinement of secretory cargo requires site-specific phosphorylation of the kinesin motor KIF17 by Ca(2+)/calmodulin-dependent protein kinases (CaMK). Thus, the length scales of early secretory trafficking in dendrites are tuned by activity-dependent regulation of microtubule-dependent transport.
authors.affiliation: Max Planck Institute for Brain Research, Frankfurt 60438, Germany. Electronic address: cyril.hanus@brain.mpg.de.
authors.forename: Cyril
authors.initials: C
authors.lastname: Hanus
authors.affiliation: Max Planck Institute for Brain Research, Frankfurt 60438, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kochen
authors.affiliation: Max Planck Institute for Brain Research, Frankfurt 60438, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Tom Dieck
authors.affiliation: Institute of Molecular & Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
authors.forename: Victor
authors.initials: V
authors.lastname: Racine
authors.affiliation: Interdisciplinary Institute for Neuroscience, Bordeaux 33077, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Sibarita
authors.affiliation: Max Planck Institute for Brain Research, Frankfurt 60438, Germany.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Schuman
authors.affiliation: Neuroscience Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA 02139, USA. Electronic address: michael.ehlers@pfizer.com.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ehlers
mesh_terms: D000818:Animals; D001692:Biological Transport; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport; D013569:Synapses / Q000378:metabolism*
chemical_list: D020409:Molecular Motor Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D016547:Kinesins