TTBK2 and Primary Cilia are Required for Purkinje Cell Survival

Abstract

Primary cilia are a small microtubule based signaling organelle. Primary cilia can be found on almost every mammalian cell, including neurons and glia. Tau Tubulin Kinase 2 (TTBK2) is a critical regulator of the building of primary cilia, and mutations within Ttbk2 cause the adult-onset, neurodegenerative disease, Spinocerebellar Ataxia type 11 (SCA11). SCA11 is characterized by a loss of Purkinje neurons throughout the cerebellum causing ataxic phenotypes in affected individuals. Given this connection, this body of work aims to define the role of primary cilia in maintaining neuron homeostasis through further defining roles of Ttbk2 both in ciliary biology as well as it’s neuronal functions. Using various genetic mouse models, I have found new roles for Ttbk2 in cilium stability and function that may help explain in part the etiology of SCA11. I then go on to further characterize the roles for primary cilia in neurons using Ttbk2 genetic knockouts. I have found that primary cilia are essential for Purkinje cell survival and have characterized a new mouse model of SCA11.