Synaptogenesis Linking to Liprin

Synaptic development requires coordinated process in both pre- and post-synaptic regions. However, much less is understood about pre-synaptic structure and function. Kaufmann et al. show that an intracellular protein called liprin interacts with the cytoplasmic domain of the receptor-type protein tyrosine phosphatase LAR in the pre-synaptic active zone of the Drosophila neuromuscular junction (NMJ). liprin was detected on both sides of the synaptic cleft but LAR was only detected in the pre-synaptic NMJ. Genetic analysis revealed that both proteins are required for normal NMJ morphogenesis, as absence of either caused a decrease in synapse size and bouton number. Absence of liprin prevented an increase in NMJ bouton number observed upon LAR overexpression, indicating that liprin acts downstream of LAR.

Synaptic transmission and pre-synaptic vesicle release was also impaired in liprin mutants. Wyszinsku et al. also report that in rat brain, liprin associated in a multi-complex with the adaptor protein GRIP and LAR. GRIP was also associated with AMPA receptors, indicting a role for liprin post-synaptic function.

Disruption of the GRIP-liprin interaction disrupted AMPA receptor clustering. Hence, liprin appears fundamental to organizing structure and function of developing synapses.

N. Kaufmann, J. DeProto, R. Ranjan, H. Wan, D. Van Vactor, Drosophila liprin-α and the receptor phosphatase Dlar control synapse morphogenesis. Neuron 34: 27-38 (2002). [Online Journal]

M. Wyszynski, E. Kim, A.W. Dunah, M. Passafaro, J.G. Valtschanoff, C. Serr-Pages, M. Streuhli, R.J. Weinberg, M. Sheng, Interaction between GRIP and liprin-α/SYD2 is required for AMPA receptor targeting. Neuron 34: 39-54 (2002). [Online Journal]