Contacts between the endoplasmic reticulum and other membranes in neurons

Abstract

Close appositions between the membrane of the endoplasmic reticulum (ER) and other intracellular membranes have important functions in cell physiology. These include lipid homeostasis, regulation of Ca 2+ dynamics, and control of organelle biogenesis and dynamics. Although these membrane contacts have previously been observed in neurons, their distribution and abundance have not been systematically analyzed. Here, we have used focused ion beam-scanning electron microscopy to generate 3D reconstructions of intracellular organelles and their membrane appositions involving the ER (distance ≤30 nm) in different neuronal compartments. ER-plasma membrane (PM) contacts were particularly abundant in cell bodies, with large, flat ER cisternae apposed to the PM, sometimes with a notably narrow lumen (thin ER). Smaller ER-PM contacts occurred throughout dendrites, axons, and in axon terminals. ER contacts with mitochondria were abundant in all compartments, with the ER often forming a network that embraced mitochondria. Small focal contacts were also observed with tubulovesicular structures, likely to be endosomes, and with sparse multivesicular bodies and lysosomes found in our reconstructions. Our study provides an anatomical reference for interpreting information about interorganelle communication in neurons emerging from functional and biochemical studies.FIB-SEM | thin ER | Stim1 | spine apparatus | subsurface cisternae

Enhanced FIB-SEM systems for large-volume 3D imaging

“…The endoplasmic reticulum (ER) is well resolved and easily segmented, allowing its full 3D structure to be extracted; one is no longer relying on sampling from 2D EM sections to infer its 3D organization. For example, the frequency of ER-to-plasma membrane and ER-to-mitochondrion contacts can be quantified across a whole cell (Wu et al, 2017), providing new insight into contact-dependent processes such as lipid transfer. Dendrites with readily-segmentable organelles, and synapses with all vesicles countable are plentiful and could be mined for statistics, for example, quantitative comparisons among synapses from the same axon, or onto the same dendrite.

10.7554/eLife.25916.014Figure 8.Isotropic high-resolution data offer easy visualization of 3D structures through arbitrary slices.( a ) Two orthoslices (x–y and x–z) from nucleus accumbens in a sample of adult mouse brain.

…”

Mitostasis in Neurons: Maintaining Mitochondria in an Extended Cellular Architecture

“…Indeed, at least in vitro, metabolic labeling with nucleotide homologues confirmed the peripheral replication of mitochondrial DNA (Amiri and Hollenbeck, 2008). Moreover, the presence of smooth ER in axons (Wu et al, 2017; Yalcin et al, 2017) signifies that the capacity for lipid synthesis is also locally available.…”

VAP‐SCRN1 interaction regulates dynamic endoplasmic reticulum remodeling and presynaptic function

“…The axonal ER structure consists of narrow ER tubules, which occasionally form cisternae at tubular branch points with comparably small lumen (Wu et al, 2017;Yalcin et al, 2017;Terasaki, 2018). This distinctive ER network extends throughout all axon branches with a relative constant density of only 1-2 narrow tubules per diameter, while remaining continuous with the rest of the ER network (Wu et al, 2017;Yalcin et al, 2017;Terasaki, 2018). At presynaptic terminals, the ER forms a local tubular network opposing the active zone.…”

“…This distinctive ER network extends throughout all axon branches with a relative constant density of only 1-2 narrow tubules per diameter, while remaining continuous with the rest of the ER network (Wu et al, 2017;Yalcin et al, 2017;Terasaki, 2018). This presynaptic ER structure often wraps around mitochondria and is in close proximity to the plasma membrane, and it regularly forms tight membrane contact sites with these structures (Wu et al, 2017;Yalcin et al, 2017). This presynaptic ER structure often wraps around mitochondria and is in close proximity to the plasma membrane, and it regularly forms tight membrane contact sites with these structures (Wu et al, 2017;Yalcin et al, 2017).…”