Presynaptic active zones in invertebrates and vertebrates

A significant controversy persists regarding the relative contributions of endocytic pathways, as CME is predominantly observed in in vitro models using non-physiological temperatures or intense stimulation, while ultrafast endocytosis appears to be the primary mechanism under physiological temperatures and in vivo conditions.

“A significant controversy persists regarding the relative contributions of these pathways, as clathrin-mediated endocytosis is predominantly observed in in vitro models using non-physiological temperatures or intense stimulation [12]. In contrast, ultrafast endocytosis appears to be the primary mechanism under physiological temperatures and in vivo conditions, suggesting that many classical”

Neurexins are expressed in thousands of isoforms due to alternative splicing, contributing to diverse synaptic properties.

“Neurexins, particularly, are expressed in thousands of isoforms due to alternative splicing, contributing to diverse synaptic properties.”

Neurexins and neuroligins guide synapse formation by specifying postsynaptic receptor composition and release probability through an extensive code of alternative splicing.

“These molecules guide synapse formation by specifying postsynaptic receptor composition and release probability through an extensive code of alternative splicing [12].”

The presynaptic active zone (AZ) is a highly specialized, electron-dense region of the presynaptic membrane crucial for rapid and efficient neurotransmitter release.

“The presynaptic active zone (AZ) is a highly specialized, electron-dense region of the presynaptic membrane crucial for rapid and efficient neurotransmitter release [11,12].”

Calcium ions play a fundamental regulatory role in orchestrating diverse endocytic processes across different synapse types.

“Calcium ions play a fundamental regulatory role in orchestrating these diverse endocytic processes across different synapse types [12].”

Bulk endocytosis is triggered by intense or prolonged neuronal stimulation and involves retrieval of large portions of the plasma membrane as large endocytic vacuoles, from which new SVs are regenerated through clathrin-mediated budding.

“Bulk endocytosis is triggered by intense or prolonged neuronal stimulation. This pathway involves the retrieval of large portions of the plasma membrane in the form of large endocytic vacuoles [30]. New SVs are subsequently regenerated from these larger structures through clathrin-mediated budding [12,31].”

CME typically occurs in the peri-active zone, adjacent to the sites of neurotransmitter release.

“CME typically occurs in the peri-active zone, adjacent to the sites of neurotransmitter release [12,28].”

Neurexins and neuroligins form heterophilic complexes that act as instructive signaling devices rather than mere structural anchors.

“Neurexins and neuroligins form heterophilic complexes that act as instructive signaling devices rather than mere structural anchors [12].”

Gi/o-mediated pathways, such as those activated by the purinergic P2Y12 receptor, provide a critical break on release probability and coordinate microglial-synapse interactions during circuit refinement.

“Furthermore, Gi/o-mediated pathways, such as those activated by the purinergic P2Y12 receptor, provide a critical break on release probability and coordinate microglial-synapse interactions during circuit refinement [1,12,45,46].”

Synapse removal is often initiated by the disengagement of SAM complexes and the cessation of their bidirectional signaling, which secondarily recruits microglia for phagocytic pruning, especially when the synaptic barcode fails to validate the connection during activity-dependent competition.

“Regarding elimination, synapse removal is often initiated by the disengagement of these SAM complexes and the cessation of their bidirectional signaling, which secondarily recruits microglia for phagocytic pruning, especially when the ‘synaptic barcode’ fails to validate the connection during activity-dependent competition [1,4,12].”