Review
Cellular and molecular insights into presynaptic assembly

https://doi.org/10.1016/S0959-4388(00)00183-5Get rights and content

Abstract

Little is known about the development of presynaptic specializations. Recent studies that visualize tagged synaptic components in cultured cells and in vivo have identified molecular participants and reveal common features in cellular processes of presynaptic assembly.

Introduction

The chemical synapse is a highly conserved structure. Despite molecular distinctions in neurotransmitter phenotype or cellular differences in terminal shape, synapses share many common ultrastructural features. In the presynaptic cell, electron-dense active zones are surrounded by accumulations of synaptic vesicles [1]. Moreover, the molecular machinery for neurotransmitter release is highly conserved across species [2], [3]. This review considers whether development of the presynaptic specialization, like its structure and function, is conserved.

Synapse formation has been studied from various approaches, including cell biology, biochemistry and the use of genetic model organisms [4], [5]. To date, we know more about postsynaptic than presynaptic development (reviewed in [6], [7]). Recent findings have begun to shed light on presynaptic assembly in diverse cell types. Here, we discuss this progress, focusing on cell biology, newly described functions of known proteins and novel proteins that participate in terminal development.

Section snippets

Definitions of ‘synaptogenesis’

Contact between a nerve and its target is followed by a series of events that includes adhesion and the appearance of specializations in each cell at regions of contact. This coordinated site is maintained, allowing cellular and molecular changes in both cell types. The terms ‘differentiation’ and ‘maturation’ are used to describe this development; however, depending on the context, these words have different meanings.

‘Differentiation’ refers to the initial development of structure and function

Cytoskeletal dynamics

An early step in synapse formation is the transition from motile growth cone to stable synapse. Actin and microtubule dynamics enable the wandering growth cone to reach its target [11]. At the target, the growth cone must stabilize. Mutations in the Drosophila genes futsch and short stop/kakapo (shot/kak) illustrate the importance of microtubule and actin dynamics in this transition. Null mutations in either of these genes preclude axon extension [12, [13]. The range of neuronal phenotypes in

Target-derived signals

What triggers the cell biological changes underlying synapse formation? A significant finding of the past year implicates neuroligin-1 in this process [45radical dot]. Neuroligins are transmembrane proteins (reviewed in [46]) that bind to PSD-95, a PDZ-domain-containing protein thought to assemble postsynaptic components at excitatory synapses [47]. Neuroligin-1 is expressed on postsynaptic cells at excitatory synapses [48]. Expression begins in the embryo, but increases throughout early postnatal

Concluding remarks

A confluence of approaches, including cell culture experiments to visualize discrete synaptic components and genetics to determine function in vivo, has provided insight into regulatory mechanisms of presynaptic development. These data show that there may be similar cell biological features that enable synaptic function shortly after contact between the presynaptic and postsynaptic cells. These findings, however, also indicate that molecular mechanisms of presynaptic assembly are not universal.

Acknowledgements

We thank Cori Bargmann for sharing unpublished data, and Aaron DiAntonio, Jeff Lichtman and Paul Taghert for thoughtful comments on the manuscript.

References and recommended reading

Papers of particular interest, published within the annual period of review,have been highlighted as:

:1(6)radical dotof special interest

radical dotradical dotof outstanding interest

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