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Review
. 2017 Mar 13:10:47.
doi: 10.3389/fnmol.2017.00047. eCollection 2017.

Molecular Mechanisms for the Coupling of Endocytosis to Exocytosis in Neurons

Affiliations
Review

Molecular Mechanisms for the Coupling of Endocytosis to Exocytosis in Neurons

Zhenli Xie et al. Front Mol Neurosci. .

Abstract

Neuronal communication and brain function mainly depend on the fundamental biological events of neurotransmission, including the exocytosis of presynaptic vesicles (SVs) for neurotransmitter release and the subsequent endocytosis for SV retrieval. Neurotransmitters are released through the Ca2+- and SNARE-dependent fusion of SVs with the presynaptic plasma membrane. Following exocytosis, endocytosis occurs immediately to retrieve SV membrane and fusion machinery for local recycling and thus maintain the homeostasis of synaptic structure and sustained neurotransmission. Apart from the general endocytic machinery, recent studies have also revealed the involvement of SNARE proteins (synaptobrevin, SNAP25 and syntaxin), synaptophysin, Ca2+/calmodulin, and members of the synaptotagmin protein family (Syt1, Syt4, Syt7 and Syt11) in the balance and tight coupling of exo-endocytosis in neurons. Here, we provide an overview of recent progress in understanding how these neuron-specific adaptors coordinate to ensure precise and efficient endocytosis during neurotransmission.

Keywords: SNARE; calmodulin; endocytosis; exocytosis; synaptotagmin; vesicle recycling.

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Figures

Figure 1
Figure 1
Schematic presentation showing proteins involved in exo-endocytosis coupling. During neurotransmission, endocytosis occurs immediately after synaptic vesicle (SV) exocytosis via clathrin-mediated endocytosis (CME), kiss-and-run and bulk endocytosis. The Ca2+-calmodulin pathway, synaptophysin (Syp) and SNARE proteins, Ca2+-binding (Syt1, Syt7) and non-Ca2+-binding (Syt4, Syt11) Syts, and other proteins such as dynamin (Dyn) coordinate to control the efficient and precise coupling of SV endocytosis to exocytosis. Syt11 is shown in red due to the nature of negative regulator, and Syt4 is shown in gray since that Syt4 shows different effects on different types fusion-fission events. Scaffolding proteins (e.g., N-BAR/F-BAR/BAR domain-containing proteins (such as FCHo, endophilin, amphiphysin, syndapin), intersectin, Rab3, CDC42, N-WASP, SNX9 and Eps15), downstream effectors (e.g., calcineurin, myosin, CDC2 and CDK5), phosphoinositide metabolism (e.g., PI(4,5)P2, cholesterol, synaptojanin, PI 3-kinase and PIPK1γ), and other general endocytic machineries (clathrin, AP-2, AP180, Epsin and stonin) are excluded to simplify the cartoon.

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