A cryo-ET survey of intracellular compartments within mammalian axons

Abstract

The neuronal axon contains many intracellular compartments which travel between the cell body and axon tip. The nature of these cargos and the complex axonal environment through which they traverse is unclear. Here, we describe the internal components of mammalian sensory axons using cryo-electron tomography. We show that axonal endoplasmic reticulum has thin, beaded appearance and is tethered to microtubules at multiple sites. The tethers are elongated, ∼ 7 nm long proteins which cluster in small groups. We survey the different membrane-bound cargos in axons, quantify their abundance and describe novel internal features including granules and broken membranes. We observe connecting density between membranes and microtubules which may correspond to motor proteins. In addition to membrane-bound organelles, we detect numerous proteinaceous compartments, including vaults and previously undescribed virus-like capsid particles. The abundance of these compartments suggests they undergo trafficking in axons. Our observations outline the physical characteristics of axonal cargo and provide a platform for identification of their constituents.