On the Teneurin track: a new synaptic organization molecule emerges - PubMed (original) (raw)

Review

On the Teneurin track: a new synaptic organization molecule emerges

Timothy J Mosca. Front Cell Neurosci. 2015.

Abstract

To achieve proper synaptic development and function, coordinated signals must pass between the pre- and postsynaptic membranes. Such transsynaptic signals can be comprised of receptors and secreted ligands, membrane associated receptors, and also pairs of synaptic cell adhesion molecules. A critical open question bridging neuroscience, developmental biology, and cell biology involves identifying those signals and elucidating how they function. Recent work in Drosophila and vertebrate systems has implicated a family of proteins, the Teneurins, as a new transsynaptic signal in both the peripheral and central nervous systems. The Teneurins have established roles in neuronal wiring, but studies now show their involvement in regulating synaptic connections between neurons and bridging the synaptic membrane and the cytoskeleton. This review will examine the Teneurins as synaptic cell adhesion molecules, explore how they regulate synaptic organization, and consider how some consequences of human Teneurin mutations may have synaptopathic origins.

Keywords: Drosophila; Teneurin; integrins; synapse development; synaptopathy.

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Figures

Figure 1

Figure 1

Molecular structure of the Teneurins. Diagram of the domain organization of the C. elegans Ten-1, the Drosophila Ten-m and Ten-a, and the human Ten-1, Ten-2, Ten-3, and Ten-4 proteins. The transmembrane domains are aligned as the reference point to facilitate comparison between the extracellular domains of each homolog. Across different species, the domain organization of the Teneurins is qualitatively similar and aligned at equivalent positions on the extracellular side. Domains were identified and mapped using NCBI sequences and domain prediction tools from SMART, Interpro, and NCBI. Each domain is color-coded (key) and scaled by size (scale = 100 amino acids). The NHL (gray) and Ca2+-binding (red) domains are shown at 65% transparency so as to indicate the dimensions of other, frequently overlapping, domains. Top = extracellular, Bottom = intracellular.

Figure 2

Figure 2

Roles for Teneurins at diverse synapses. (A) Teneurin function at the Drosophila neuromuscular junction (NMJ). Ten-a in the presynaptic motoneuron and Ten-m in the postsynaptic muscle interact transsynaptically to organize the cytoskeleton and ensure active zone apposition with glutamate receptors (Mosca et al., 2012). (B) Teneurin function in the Drosophila CNS. Ten-a in presynaptic olfactory receptor axons interacts transsynaptically with Ten-m in postsynaptic projection neuron dendrites to organize the spectrin cytoskeleton and ensure proper active zone and acetylcholine receptor number (Mosca and Luo, 2014). It is unknown whether postsynaptic Ten-m also regulates cytoskeletal organization (question mark). (C) Two models of Teneurin function in hippocampal neurons. On the left, Teneurin-2 is a postsynaptic receptor for Latrophilin (Silva et al., 2011). The downstream mechanisms that ensure synaptic organization and function on both sides remain unknown (question marks). On the right, Ten-1 interacts with β-Dystroglycan (β-DG) to activate a MEK/ERK pathway resulting in cytoskeletal rearrangement (Chand et al., 2012). The source of Ten-1, is unknown; though hypothesized to be postsynaptic, it could also be presynaptic (question mark). (D) A potential model for Teneurin signaling with integrins at the Drosophila NMJ. Ten-m and αPS2 interact (Graner et al., 1998), and PGANT3 and PGANT35A regulate Ten-m and integrin levels, leading to normal synaptic function (Dani et al., 2014). Ten-m has a minor presynaptic role (Mosca et al., 2012), and could interact with αPS2 either in cis or trans; as such, both models are presented (question mark). It is currently unclear how these interactions enable cell adhesion, synaptic organization, and function.

Figure 3

Figure 3

A Model for homo- vs. heterophilic Teneurin signaling via tension. A model (adapted from Beckmann et al., 2013) for how tension created by homophilic vs. heterophilic Teneurin interactions could distinguish partner matching from synaptic organization. The enhanced strength of homophilic interactions (left) alters cytoskeletal dynamics on the pre- and postsynaptic sides, activating signaling pathways that transition growth cones from exploring neurites to structures amenable to synapse formation. Weaker heterophilic interactions (right) regulate cytoskeletal organization and active zone apposition, leading to synaptic organization via signaling mechanisms distinct from partner matching.

References

    1. Abuelo D. N., Ahsanuddin A. N., Mark H. F. (2000). Distal 5q trisomy resulting from an X;5 translocation detected by chromosome painting. Am. J. Med. Genet. 94, 392–399. 10.1002/1096-8628(20001023)94:5<392::aid-ajmg10>3.0.co;2-h -DOI -PubMed
    1. Ahmed W. W., Li T. C., Rubakhin S. S., Chiba A., Sweedler J. V., Saif T. A. (2012). Mechanical tension modulates local and global vesicle dynamics in neurons. Cell. Mol. Bioeng. 5, 155–164. 10.1007/s12195-012-0223-1 -DOI -PMC -PubMed
    1. Al Chawaf A., St Amant K., Belsham D., Lovejoy D. A. (2007). Regulation of neurite growth in immortalized mouse hypothalamic neurons and rat hippocampal primary cultures by teneurin C-terminal-associated peptide-1. Neuroscience 144, 1241–1254. 10.1016/j.neuroscience.2006.09.062 -DOI -PubMed
    1. Aldahmesh M. A., Mohammed J. Y., Al-Hazzaa S., Alkuraya F. S. (2012). Homozygous null mutation in ODZ3 causes microphthalmia in humans. Genet. Med. 14, 900–904. 10.1038/gim.2012.71 -DOI -PubMed
    1. Antinucci P., Nikolaou N., Meyer M. P., Hindges R. (2013). Teneurin-3 specifies morphological and functional connectivity of retinal ganglion cells in the vertebrate visual system. Cell Rep. 5, 582–592. 10.1016/j.celrep.2013.09.045 -DOI -PMC -PubMed

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