While this route to the PM has received little direct evidence beyond static EM micrographs, it would represent a unique, noncanonical trafficking route to the plasma membrane that bypasses Golgi membranes and may help explain how membrane proteins could be locally trafficked in dendrites lacking Golgi outposts. Interestingly the SA is missing in mice lacking synaptopodin, an actin-associated

protein of unknown function that normally localizes to this organelle. Mice lacking synaptopodin have impaired hippocampal long-term potentiation (LTP) and spatial learning deficits, underscoring the importance of this SER-derived organelle (Deller et al., 2003). In addition to ER and Golgi-derived membranes, endosomes are abundant in dendritic arbors selleck chemical from diverse neuronal subtypes (Cooney et al., selleckchem 2002) (Figure 1B). Endosomes are

intracellular membranous compartments up to several microns in size that accept internalized vesicles from the plasma membrane and ultimately sort membrane-associated cargo for recycling back to the plasma membrane or for lysosomal degradation. The endosomal network comprises early/sorting endosomes (ESEs), recycling endosomes (REs), late endosomes (LEs), and lysosomes (Maxfield and McGraw, 2004). Newly formed vesicles originating form the plasma membrane fuse with one another and with ESEs, which have tubulovesicular morphology. ESEs then progress to LEs over the course of minutes as they become more acidic and gain hydrolase activity leading to degradation of remaining cargo (Maxfield and McGraw, 2004). Prior to the LE transition, cargoes destined for recycling exit ESEs and fuse directly with the plasma membrane or with REs (Dunn et al., 1989 and Mayor et al., 1993). In dendrites, REs are present within or at the base of ∼70% of spines (Cooney et al., 2002 and Park et al., 2004), suggesting that localized endosomal trafficking

takes place throughout dendrites and that a majority of synapses CYTH4 are associated with at least one nearby endosomal compartment (Figure 1B). Functional evidence for endosome involvement in trafficking synaptic molecules has come from studies on α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-type glutamate receptors (Beattie et al., 2000, Carroll et al., 1999, Ehlers, 2000 and Lin et al., 2000). Direct activation of these receptors with AMPA leads to rapid internalization and degradation while brief activation of N-methyl D-aspartate (NMDA)-type glutamate receptors causes internalization and subsequent reinsertion of AMPA receptors into the dendritic PM (Ehlers, 2000). These data highlight the involvement of the dendritic endosomal network in AMPA receptor trafficking and point to REs as potential dendritic storehouses of synaptic proteins.