Local Zones of Endoplasmic Reticulum Complexity Confine Cargo in Neuronal Dendrites

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. [Display omitted] ► The endoplasmic reticulum (ER) in dendrites shows spatial variation in complexity ► Increased complexity occurs at dendritic branch points, confining membrane cargo ► An mGluR/PKC/CLIMP63 pathway bidirectionally regulates ER complexity ► ER complexity controls dendritic morphogenesis and defines sites of branch formation The endoplasmic reticulum forms a continuous network within neuronal dendrites, but its morphological complexity varies from one dendritic region to another. Membrane proteins such as receptors and ion channels become trapped in regions of high complexity, influencing the formation and distinct functional properties of the dendritic segments proximal to these regions of the ER.