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Molecular Organization and Assembly of the Presynaptic Active Zone of Neurotransmitter Release

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Cell Communication in Nervous and Immune System

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 43))

Abstract

At chemical synapses, neurotransmitter is released at a restricted region of the presynaptic plasma membrane, called the active zone. At the active zone, a matrix of proteins is assembled, which is termed the presynaptic grid or cytomatrix at the active zone (CAZ). Components of the CAZ are thought to localize and organize the synaptic vesicle cycle, a series of membrane trafficking events underlying regulated neurotransmitter exocytosis. This review is focused on a set of specific proteins involved in the structural and functional organization of the CAZ. These include the multi-domain Rab3-effector proteins RIM1α and RIM2α; Bassoon and Piccolo, two multi-domain CAZ scaffolding proteins of enormous size; as well as members of the CAST/ERC family of CAZ-specific structural proteins. Studies on ribbon synapses of retinal photoreceptor cells have fostered understanding the molecular design of the CAZ. In addition, the analysis of the delivery pathways for Bassoon and Piccolo to presynaptic sites during development has produced new insights into assembly mechanisms of brain synapses during development. Based on these studies, the active zone transport vesicle hypothesis was formulated, which postulates that active zones, at least in part, are pre-assembled in neuronal cell bodies and transported as so-called Piccolo-Bassoon transport vesicles (PTVs) to sites of synaptogenesis. Several PTVs can fuse on demand with the presynaptic membrane to rapidly form an active zone.

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Abbreviations

C1 domain:

conserved domain 1 of protein kinase C

C2 domain:

conserved domain 2 of protein kinase C

CAST:

CAZ-associated structural protein

CAZ:

cytomatrix assembled at the active zone

CtBP:

C-terminal binding protein (or connected to Bassoon and Piccolo)

DAG:

diacylglycerol

ERC:

ELKS-Rab6-interacting molecule-CAST

GIT:

protein interacting with G-protein-coupled receptor kinases

PBH domain:

Piccolo-Bassoon homology domain

PDZ:

PSD-95-Discs large-ZO-1 domain

PSD:

postsynaptic density

PTV:

Piccolo-Bassoon transport vesicle

RIM:

Rab3-interacting molecule

RIM-BP:

RIM-binding protein

SV:

synaptic vesicle

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Acknowledgments

Work on active zone function and assembly in the authors' lab is supported by the Deutsche Forschungsgemeinschaft, the European Commission (SynScaff), the Swiss National Fonds, the Fonds der Chemischen Industrie and the Max Planck Prize awarded by the Alexander von Humboldt Foundation and the Max Planck Society.

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  1. Leibniz Institute for Neurobiology, Department of Neurochemistry and Molecular Biology, Brennecke Str. 6, 39118, Magdeburg, Germany

    Anna Fejtova & Eckart D. Gundelfinger

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  1. Anna Fejtova
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Correspondence to Anna Fejtova .

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Eckart D. Gundelfinger Constanze I. Seidenbecher Burkhart Schraven

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Fejtova, A., Gundelfinger, E.D. (2006). Molecular Organization and Assembly of the Presynaptic Active Zone of Neurotransmitter Release. In: Gundelfinger, E.D., Seidenbecher, C.I., Schraven, B. (eds) Cell Communication in Nervous and Immune System. Results and Problems in Cell Differentiation, vol 43. Springer, Berlin, Heidelberg . https://doi.org/10.1007/400_012

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