Although we already have a good picture of how the postsynaptic zone is built, our knowledge of the presynaptic terminal is less sophisticated. How the presynaptic bouton is put together remains largely a mystery, although we know some of the building blocks and have begun to unravel their molecular interactions. A recent paper by Kaufmann and her colleagues provides us with new clues about presynaptic assembly by showing that the protein Liprin-α controls synapse morphogenesis in Drosophila.

In mammalian cells, liprin-α interacts with tyrosine phosphatases of the LAR family. This observation prompted Kaufmann et al. to test whether the Drosophila protein Lar showed a similar interaction. Indeed, they identified the fly homologue of liprin-α, and showed that the neuromuscular junctions of Liprin-α mutants have morphological and functional abnormalities. Importantly, the authors found similar abnormalities in Lar mutant flies, and a genetic analysis led them to conclude that the two molecules participate in the regulation of presynaptic morphogenesis as parts of the same pathway.

But not all of the action takes place presynaptically; in a related paper, Wyszynski et al. report that liprin-α participates in postsynaptic receptor targeting in mammalian neurons.

Looking for proteins that could interact with GRIP, a postsynaptic scaffold protein, the authors isolated liprin-α, and found it as part of a complex that included GRIP, AMPA receptors and a LAR phosphatase. What is the meaning of these interactions? As a first step to answering this question, Wyszynski and his colleagues disrupted the association between liprin-α and GRIP, and found that the targeting and surface expression of AMPA receptors was impaired.

The two papers point to a role for liprin-α in synaptic organization on both sides of the cleft. Although many questions about this process remain unanswered, the participation of LAR phosphatases stands out. Do they have a signalling function? If so, what are the relevant downstream molecules? We are still a long way from understanding this aspect of synaptogenesis.