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Publication - Professor Jonathan Hanley

    PICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity


    Nakamura, Y, Wood, C, Patton, A, Jaafari, N, Henley, J, Mellor, J & Hanley, J, 2011, ‘PICK1 inhibition of the Arp2/3 complex controls dendritic spine size and synaptic plasticity’. EMBO Journal, vol 30 ., pp. 719 - 730


    Activity-dependent remodelling of dendritic spines is essential for neural circuit development and synaptic plasticity, but the precise molecular mechanisms that regulate this process are unclear. Activators of Arp2/3- mediated actin olymerisation are required for spine enlargement; however, during long-term depression (LTD), spines shrink via actin depolymerisation and Arp2/3 inhibitors in this process have not yet been identified. Here, we show that PICK1 regulates spine size in hippocampal neurons via inhibition of the Arp2/3 complex. PICK1 knockdown increases spine size, whereas PICK1 overexpression reduces spine size. NMDA receptor activation results in spine shrinkage, which is blocked by PICK1 knockdown or overexpression of a PICK1 mutant that cannot bind Arp2/3. Furthermore, we show that PICK1– Arp2/3 interactions are required for functional hippocampal LTD. This work demonstrates that PICK1 is a novel regulator of spine dynamics. Via Arp2/3 inhibition, PICK1 has complementary yet distinct roles during LTD to regulate AMPA receptor trafficking and spine size, and therefore functions as a crucial factor in both structural and functional plasticity.

    Full details in the University publications repository