The impact of cytoskeletal organization on the local regulation of neuronal transport

Abstract

Neurons are akin to modern cities in that both are dependent on robust transport mechanisms. Like the best mass transit systems, trafficking in neurons must be tailored to respond to local requirements. Neurons depend on both high-speed, long-distance transport and localized dynamics to correctly deliver cargoes and to tune synaptic responses. Here, we focus on the mechanisms that provide localized regulation of the transport machinery, including the cytoskeleton and molecular motors, to yield compartment-specific trafficking in the axon initial segment, axon terminal, dendrites and spines. The synthesis of these mechanisms provides a sophisticated and responsive transit system for the cell.

F‐actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes

“…Plasticity and stability of synaptic contacts rely on several factors, including transport and delivery of proteins and mRNA from the soma, local dendritic protein synthesis, surface diffusion of membrane proteins, recycling of synaptic proteins via the dendritic secretory trafficking system, and controlled disposal of “aged” molecules mediated by lysosomes, autophagosomes, and the proteasomal system (Hanus & Schuman, ; Mikhaylova et al , ; Bowen et al , ; Goo et al , ; Nirschl et al , ; Penn et al , ; Seipold et al , ). Various secretory trafficking organelles are present along dendrites and help to regulate the protein pool required for potentiation and stabilization of specific synaptic contacts (van Bommel & Mikhaylova, ).…”

Activity-dependent nucleation of dynamic microtubules at presynaptic boutons is required for neurotransmission

“…Classic electron microscopy studies have described the presence of pools of MTs at presynaptic sites in the rat cortex and cerebellum, including synaptic vesicle (SV)-clothed MTs attached to the active zone and peripheral coils of MTs in close contact with presynaptic mitochondria (10)(11)(12)(13)(14)(15)(16). These observations suggested that presynaptic MTs may be functionally coupled with synaptic transmission by: (1) driving the interbouton translocation of SVs (2) maintaining the organization of the presynaptic active zone (AZ), (3) contributing to the maturation of postsynaptic receptors by conveying new SVs to be released at certain presynaptic sites (17), (4) anchoring mitochondria at sites of release (14,18). Few studies, however, have explored these possibilities using modern imaging approaches.…”

Neuronal functions of adaptor complexes involved in protein sorting

“…For instance, to the already described function of AP-2 in coupling dynein-dynactin to autophagosomes for retrograde transport along the axon 34], we can add the interaction of AP-1 with kinesins for anterograde transport of TGN- or endosome-derived carriers [61,62]. This function would be akin to that of other adaptors that link organelles to microtubule motors [3]. Fully elucidating both the canonical and non-canonical functions of AP complexes in neurons will be essential to explain the pathogenesis of AP coatopathies that affect the central nervous system.…”

“…The establishment and maintenance of this heterogeneous distribution of intracellular components rely on a variety of molecular mechanisms that deliver them to their corresponding neuronal locations. For organelles, selective transport depends on adaptor proteins that couple them to cytoskeletal motors, a subject that has been covered in previous reviews [1,2,3]. On the other hand, the sorting of specific proteins to different locations is controlled by a different set of adaptors that mediate incorporation of the proteins into specific populations of transport carriers [1,4].…”