title: Local zones of endoplasmic reticulum complexity confine cargo in neuronal dendrites.
abstract: Following synthesis, integral membrane proteins dwell in the endoplasmic reticulum (ER) for variable periods that are typically rate limiting for plasma membrane delivery. In neurons, the ER extends for hundreds of microns as an anastomosing network throughout highly branched dendrites. However, little is known about the mobility, spatial scales, or dynamic regulation of cargo in the dendritic ER. Here, we show that membrane proteins, including AMPA-type glutamate receptors, rapidly diffuse within the continuous network of dendritic ER but are confined by increased ER complexity at dendritic branch points and near dendritic spines. The spatial range of receptor mobility is rapidly restricted by type I mGluR signaling through a mechanism involving protein kinase C (PKC) and the ER protein CLIMP63. Moreover, local zones of ER complexity compartmentalize ER export and correspond to sites of new dendritic branches. Thus, local control of ER complexity spatially scales secretory trafficking within elaborate dendritic arbors.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.forename: Cyril
authors.initials: C
authors.lastname: Hanus
authors.forename: Tao
authors.initials: T
authors.lastname: Cui
authors.forename: Thomas
authors.initials: T
authors.lastname: Helton
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bourne
authors.forename: Deborah
authors.initials: D
authors.lastname: Watson
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Harris
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ehlers
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003712:Dendrites / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: C554951:CKAP4 protein, rat; D008565:Membrane Proteins; D018091:Receptors, AMPA; D011956:Receptors, Cell Surface; D018094:Receptors, Metabotropic Glutamate; D011493:Protein Kinase C