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Proteomic analysis of the presynaptic active zone

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Abstract

Synaptic vesicles are key organelles in chemical signaling, allowing neurons to communicate with each other and with neighboring cells. Vesicle integral or membrane-associated proteins mediate the various tasks the organelle fulfills during its life cycle. These include organelle transport, interaction with the nerve terminal cytoskeleton, uptake and storage of low molecular weight constituents, and the regulated interaction with the presynaptic plasma membrane, the active zone, during exo- and endocytosis. Converging work from several laboratories within the last 30 years resulted in the molecular and functional characterization of the protein inventory of the synaptic vesicle compartment. Nowadays advances in membrane protein separation and mass spectrometry have dramatically promoted this field resulting in a detailed description of the synaptic vesicle proteome and making synaptic vesicles the best characterized organelles. Recently, the proteome of the active zone was identified using the docked synaptic vesicles as target for immunoisolation. Combining gel-based protein separation techniques, mass spectrometry, and immunodetection, a considerable variety of proteins has been detected in the active zone. This includes synaptic vesicle proteins, components of the presynaptic fusion and retrieval machinery, proteins involved in intracellular signal transduction, a large variety of adhesion molecules and proteins potentially involved in regulating the functional and structural dynamics of the presynapse. Here, we discuss recent information concerning the proteome of the presynaptic active zone, focusing on proteins that are potentially involved in the short- and long-term structural modulation of the mature presynaptic compartment. In addition, we discuss the functional relevance of amyloid precursor protein in these membrane fractions and the putative interplay with direct or indirect interaction partners in the active zone.

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Abbreviations

APP:

Amyloid precursor protein

APLP1:

Amyloid precursor-like protein 1

APLP2:

Amyloid precursor-like protein 2

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Acknowledgments

Financial support was provided by the Deutsche Forschungsgemeinschaft (FOR1332/TP4). We are grateful to Melanie Laßek und Jens Weingarten for valuable suggestions and providing Fig. 1, 2, and 3. We are indebted to Dr. Herbert Zimmermann for critically reading of the manuscript.

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  1. Neurochemistry, Institute for Cell Biology and Neuroscience, Goethe University, Max-von-Laue-Str. 13, 60438, Frankfurt am Main, Germany

    W. Volknandt

  2. Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt am Main, Germany

    M. Karas

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Correspondence to W. Volknandt.

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Volknandt, W., Karas, M. Proteomic analysis of the presynaptic active zone. Exp Brain Res 217, 449–461 (2012). https://doi.org/10.1007/s00221-012-3031-x

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