aVolado, an Integrin involved in learning and memory, as well as PS-Integrins regulate synaptic plasticity in Drosophila

# Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK, % Department of Biology, University of Utah, Salt Lake City, UT 84112, @ Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030,

Work on different model systems suggests that Integrins play a role in the development and function of the nervous system. Here we provide first genetic proof for this hypothesis. We show that four different Drosophila Integrins are expressed in the postembryonic NMJ concurrent with the onset of morphological and physiological synaptic plasticity; a b-(bPS), and three a-Integrins (aPS1, aPS2 and aVolado). The three PS-Integrins are constitutively expressed on the postsynaptic side, only bPS might also be localised presynaptically. In contrast, aVolado protein accumulates in presynaptic boutons in a transient and highly dynamic fashion under negative neural activity-dependent regulation. Null volado mutants die as severely uncoordinated larvae and show morphological overgrowth at the NMJ suggesting that aVolado functions as an activity-dependent STOP signal for synaptic sprouting. In contrast, hypomorphic myospheroid (bPS) mutants which also die as uncoordinated larvae show the opposite morphological defect of undergrowth at the NMJ. At the ultrastructural level only volado mutant NMJs show defects; in contrast to wild type, vesicle densities in motorneuronal boutons of volado mutant larvae do not increase. Furthermore, synaptic transmission characteristics are weakened in volado mutant larvae. Thus, we provide genetic proof that Drosophila Integrins are required for at least three aspects of postembryonic NMJ development; the control of growth, of vesicle density and of transmission characteristics at the synapse. Similar synaptic features have been discussed in the context of learning in other model systems, and we propose that learning/memory defects in volado mutant flies (X.-R.Z. and R.D, manuscript submitted) are due to defects at brain synapses which are comparable to those found at the NMJ.