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Understanding the subcellular distribution and interactions of teneurins


The emergence of synaptic specificity during brain development is driven by protein interactions at the synaptic membrane, such as cell adhesion molecule interactions. Although many cell adhesion molecules are implicated in the process, teneurins, a family of type II transmembrane glycoproteins, are key mediators. They are highly conserved between species and widely expressed across interconnected areas during development, regulating key neurodevelopmental processes during connectivity establishment.  Four teneurin paralogues are found in vertebrates yet their subcellular distribution in neurons and the way these paralogues interact with each other is unknown.

In a new publication in Frontiers in Neuroscience from the Hindges lab, Angela Cheung and colleagues investigate teneurin distribution and interactions between paralogues. In their work, Cheung et al. fluorescently tagged the four paralogues to track them in cultured neurons or brain slices and found that all the teneurins can be found in a punctate distribution and partially localised to synapses. Each teneurin paralogue was differentially dispersed across distinct pre- and postsynaptic sites and Tenm3 was found to be localised to specific substructures in dendritic spines of CA1 neurons. Cheung et al.’s work further showed that the intracellular domain of teneurin plays an important role for synaptic localisation.

Contrary to previous work, Cheung et al. found that all the teneurins are able to form the full complement of homodimers and cis-heterodimers. This finding is significant as it suggests that the repertoire of distinct molecular teneurin complexes to drive synaptic specificity is even larger than previously understood. 

Cheung et al.’s work, funded by the Leverhulme Trust and the MRC, offers new insights into the distribution and activity of key synaptic specificity factors. Furthermore, their work has biomedical relevance through the emerging association between teneurins, cancers and neurological disorders, including depression, schizophrenia and bipolar disorder.