LATS2 modulates synaptic organization and function by regulating actin dynamics

Abstract

Recent work has highlighted the importance of core Hippo pathway kinases in cycling cells. Many of these kinases are also expressed in post-mitotic neurons, where they have been linked to synaptic function, and more recently a number have been shown to be dysregulated in neurodegenerative diseases such as Alzheimers disease. Despite this, little is known about the specific role or subcellular localization of the Large Tumor Suppressor kinases, LATS1 and LATS2, in postmitotic neurons. Previously, we demonstrated that LATS1 plays an important role in synapse development; however, the role of LATS2 remains poorly understood. Here, we examined the distribution and function of LATS2 and found that it is highly expressed in CA3/CA4 neurons of the hippocampus and localized throughout dendrites and dendritic spines. In contrast to LATS1, LATS2 expression remains stable throughout neuronal development. Furthermore, ectopic expression of LATS2 induces kinase-dependent structural spine defects, alters actin dynamics and reduces activity-dependent synaptic SEP-GluR1 fluorescence. Collectively, these findings reveal a unique distribution LATS2 in the hippocampus and demonstrate that LATS2 directly regulates actin dynamics and GluR1-containing AMPAR trafficking.