Abstract
Neurons face the challenge of regulating the abundance, distribution and repertoire of integral membrane proteins within their immense, architecturally complex dendritic arbors. While the endoplasmic reticulum (ER) supports dendritic translation, most dendrites lack the Golgi apparatus (GA), an essential organelle for conventional secretory trafficking. Thus, whether secretory cargo is locally trafficked in dendrites through a non-canonical pathway remains a fundamental question. Here we define the dendritic trafficking itinerary for key synaptic molecules in rat cortical neurons. Following ER exit, the AMPA-type glutamate receptor GluA1 and neuroligin 1 undergo spatially restricted entry into the dendritic secretory pathway and accumulate in recycling endosomes (REs) located in dendrites and spines before reaching the plasma membrane. Surprisingly, GluA1 surface delivery occurred even when GA function was disrupted. Thus, in addition to their canonical role in protein recycling, REs also mediate forward secretory trafficking in neuronal dendrites and spines through a specialized GA-independent trafficking network.
Highlights
Neurons face the challenge of tuning protein levels in dendritic processes that can project hundreds of micrometers from their cell bodies
Following delivery to the PM, both GluA1 and neuroligin 1 (NL1) localized to dendrites and spines, consistent with previous reports using tagged expression constructs and their associated fluorescent proteins were sensitive to thrombin treatment (Figure 1F, Figure 1—figure supplements 2 and 3) (Chih et al, 2006; Patterson et al, 2010)
Dendritic recycling endosomes mediate anterograde trafficking in dendrites We investigated the fate of secretory cargo following ER-Golgi intermediate compartments (ERGICs) exit
Summary
Neurons face the challenge of tuning protein levels in dendritic processes that can project hundreds of micrometers from their cell bodies. MRNAs encoding thousands of different proteins are found in dendrites (Cajigas et al, 2012), where their regulated translation is critical for neuronal dendrite development, maintenance and plasticity (Sutton and Schuman, 2006; Bramham and Wells, 2007; Hanus and Schuman, 2013). Many of these dendritic mRNAs encode secreted factors and critical integral membrane proteins, implying the presence of a satellite secretory system for local processing and trafficking of newly synthesized cargo. Whether dendrites can support local secretory trafficking in the absence of GA and if so, the identity and spatial distribution of the organelles responsible have remained fundamental issues
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
