ROLE OF LARGE TUMOR SUPPRESSOR PROTEINS (LATS1/2) IN NEURONAL MATURATION

Abstract

The large tumor suppressor kinases (LATS1/2) are core kinases of the Hippo pathway. Little is known about their expression in the mature CNS. Here we show that Scribble can precipitate LATS2 protein from rat adult hippocampal lysate and that phosphorylated LATS (pLATS) and Scribble localize to the axon initiation segment (AIS) in hippocampal neurons. Using STED microscopy, we find that both Scribble and pLATS form distinct puncta with the Scribble puncta being190nm apart, similar to the pLATS puncta. Overexpression of myc-LATS2 and using a novel CRISPR dependent approach to label endogenous LATS2 with GFP, reveal that LATS2 is enriched in dendritic spines. Next, we developed a conditional approach to reduce LATS proteins in post mitotic neurons – this was unsuccessful. Nonetheless, this work identifies that LATS2 is expressed in hippocampal synapses, implicating it as an important kinase in learning and memory.