WIP Is a Negative Regulator of Neuronal Maturation and Synaptic Activity

Wiskott–Aldrich syndrome protein (WASP) –interacting protein (WIP) is an actin-binding protein involved in the regulation of actin polymerization in cells, such as fibroblasts and lymphocytes. Despite its recognized function in non-neuronal cells, the role of WIP in the central nervous system has not been examined previously. We used WIP-deficient mice to examine WIP function both in vivo and in vitro. We report here that WIP−/− hippocampal neurons exhibit enlargement of somas as well as overgrowth of neuritic and dendritic branches that are more evident in early developmental stages. Dendritic arborization and synaptogenesis, which includes generation of postsynaptic dendritic spines, are actin-dependent processes that occur in parallel at later stages. WIP deficiency also increases the amplitude and frequency of miniature excitatory postsynaptic currents, suggesting that WIP−/− neurons have more mature synapses than wild-type neurons. These findings reveal WIP as a previously unreported regulator of neuronal maturation and synaptic activity.Grants from Consejo Superior de Investigaciones Cientı´ficasComunidad de Madrid (CCG08-CSIC/SAL-3471), CSIC (PIE2- 00720I002), and the Spanish Ministry of Education and Science (BFU2007-64144 and BFU2010-21374) to I.M.A., from Centro de Investigacio´n Biome´dica en Red Enfermedades Neurodegenerativas (Instituto de Salud Carlos III), the Plan Nacional DGCYT (SAF2009-12249-C02-01) to F.W. and SAF2010-15676 to S.K., and by an institutional grant from the Fundacio´n Ramo´n Areces. A.F. was a recipient of an FPU MEC fellowship (AP2005-3405), I.B. held a contract from the Comunidad Auto´noma de Madrid and S.K., a Ramo´n y Cajal contract.Peer reviewe