Functional inhibition of katanin affects synaptic plasticity

Abstract

Dynamic microtubules critically regulate synaptic functions, but the role of microtubule severing in these processes is barely understood. Katanin is a neuronally expressed microtubule-severing complex regulating microtubule number and length in cell division or neurogenesis, however its potential role in synaptic functions has remained unknown. Studying mice from both sexes, we found that katanin is abundant in neuronal dendrites and can be detected at individual excitatory spine synapses. Overexpression of a dominant-negative ATPase-deficient katanin subunit to functionally inhibit severing, alters the growth of microtubules in dendrites, specifically at premature but not mature neuronal stages without affecting spine density. Notably, interference with katanin function prevented structural spine remodeling following single synapse glutamate uncaging and significantly affected the potentiation of AMPA-receptor-mediated excitatory currents after chemical induction of long-term potentiation. Furthermore, katanin inhibition reduced the invasion of microtubules into fully developed spines. Our data demonstrate that katanin-mediated microtubule-severing regulates structural and functional plasticity at synaptic sites.Significance StatementExcitatory spine synapses are rich in actin filaments that critically regulate structural and functional synaptic plasticity.In contrast, microtubules just transiently polymerize into dendritic spines. A synaptic role of dynamic microtubules is incompletely understood and the mechanisms that regulate microtubule rearrangement at synaptic sites have remained largely unknown. Here, we show that the microtubule severing enzyme katanin, known to keep microtubules in a dynamic state, is a component of synapses mediating functional and structural roles. Our data highlight an unnoted player of synapse function and connect microtubule severing with synaptic plasticity.