About this Research Topic
Synapses are a fundamental component of neuronal transmission in behaving organisms. The understanding of their formation, structural composition, and function has evolved drastically in the last decades. New molecular and genetic tools, microscopy, and optogenetic approaches have enabled fundamental insights into how synaptic biology is tied to the cell biology of the neuron.
Already at the time of Heuser and Reese, comparative approaches of synaptic biology in different model organisms, in vivo and in vitro have yielded fundamental conserved insights into the cell biology of the synapse.
Although we have gained a tremendous amount of knowledge many challenges and questions remain. One area that is making tremendous strides in research on neuronal trafficking essential for synapse development, function, and maintenance. Recent advances in proteomics and new-generation sequencing have enabled a better assessment of which synaptic proteins are translated at synapses or at the soma of neurons. These studies have lain out the groundwork to follow up on what signaling and mechanisms could establish these categories. Optical spatiotemporal control of molecular motors or secretory trafficking studies have revealed that synaptic activity plays a key role in controlling trafficking both subcellularly and at the plasma membrane.
The combination of live imaging and EM are also revealing in more detail how the spatial organization of subcellular organelles such as ER and mitochondria matter for trafficking of pre- and post-synaptic proteins.
Furthermore, comparative approaches using advanced genetic tools in model organisms and cell cultures are identifying fundamentally conserved developmental principles and protein interaction motifs essential for synapse formation and maintenance.
Finally, liquid-liquid phase separation, or LLPS, has also started to become an important concept in synaptic trafficking. As such the organization principles of LLPS which can be applied to the presynaptic active zone, and both excitatory and inhibitory postsynaptic densities, can help understand how scaffold or membrane proteins are trafficked to synapses. More specifically whereas previous targeting of proteins was based on specific protein-protein interactions, delivery, and incorporation into LLPS seem to follow less stringent requirements of protein-protein interaction and be based more on the overall ability to interact with protein complexes based on charge, hydrophobicity, or a specific combination of both.
Overall, new tools, concepts, and comparative approaches are driving new questions specific to the trafficking of synaptic components.
Some of the key questions being asked are:
O How is compartment-specific (axon, or dendrite) trafficking regulated for synapse formation?
O What are the signaling pathways required for synaptic maintenance?
O What are the differences in trafficking components involved in establishing synapses, maintaining them, or synaptic plasticity?
O How much is dependent on cell or synaptic activity and how much not?
The goal of this Research Topic is to bring together different and complementary approaches to tackle some of these questions by using in vivo, in vitro, and modeling approaches aiming to paint a mechanistic and cell biological view of the role of trafficking in synaptic biology.
Specifically, we aim to cover the following themes within the context of synaptic development maintenance, and plasticity processes:
Trafficking of presynaptic and postsynaptic components:
o Delivery strategies
o Maintenance strategies
o Participation of degradation in synaptic homeostasis
The role of trans-synaptic signaling in synaptic trafficking regulation.
The role of phase separation as an emerging mechanism for synaptic trafficking and retention.
The role of ER and mitochondria in trafficking regulation at synapses
Already at the time of Heuser and Reese, comparative approaches of synaptic biology in different model organisms, in vivo and in vitro have yielded fundamental conserved insights into the cell biology of the synapse.
Although we have gained a tremendous amount of knowledge many challenges and questions remain. One area that is making tremendous strides in research on neuronal trafficking essential for synapse development, function, and maintenance. Recent advances in proteomics and new-generation sequencing have enabled a better assessment of which synaptic proteins are translated at synapses or at the soma of neurons. These studies have lain out the groundwork to follow up on what signaling and mechanisms could establish these categories. Optical spatiotemporal control of molecular motors or secretory trafficking studies have revealed that synaptic activity plays a key role in controlling trafficking both subcellularly and at the plasma membrane.
The combination of live imaging and EM are also revealing in more detail how the spatial organization of subcellular organelles such as ER and mitochondria matter for trafficking of pre- and post-synaptic proteins.
Furthermore, comparative approaches using advanced genetic tools in model organisms and cell cultures are identifying fundamentally conserved developmental principles and protein interaction motifs essential for synapse formation and maintenance.
Finally, liquid-liquid phase separation, or LLPS, has also started to become an important concept in synaptic trafficking. As such the organization principles of LLPS which can be applied to the presynaptic active zone, and both excitatory and inhibitory postsynaptic densities, can help understand how scaffold or membrane proteins are trafficked to synapses. More specifically whereas previous targeting of proteins was based on specific protein-protein interactions, delivery, and incorporation into LLPS seem to follow less stringent requirements of protein-protein interaction and be based more on the overall ability to interact with protein complexes based on charge, hydrophobicity, or a specific combination of both.
Overall, new tools, concepts, and comparative approaches are driving new questions specific to the trafficking of synaptic components.
Some of the key questions being asked are:
O How is compartment-specific (axon, or dendrite) trafficking regulated for synapse formation?
O What are the signaling pathways required for synaptic maintenance?
O What are the differences in trafficking components involved in establishing synapses, maintaining them, or synaptic plasticity?
O How much is dependent on cell or synaptic activity and how much not?
The goal of this Research Topic is to bring together different and complementary approaches to tackle some of these questions by using in vivo, in vitro, and modeling approaches aiming to paint a mechanistic and cell biological view of the role of trafficking in synaptic biology.
Specifically, we aim to cover the following themes within the context of synaptic development maintenance, and plasticity processes:
Trafficking of presynaptic and postsynaptic components:
o Delivery strategies
o Maintenance strategies
o Participation of degradation in synaptic homeostasis
The role of trans-synaptic signaling in synaptic trafficking regulation.
The role of phase separation as an emerging mechanism for synaptic trafficking and retention.
The role of ER and mitochondria in trafficking regulation at synapses
Keywords: trafficking, vesicular transport, local translation, phase separation, plasticity, endo- and exocytosis, cytoskeleton, spatio-temporal mechanisms, synaptic protein homeostasis
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