TTBK2 and primary cilia are essential for the connectivity and survival of cerebellar Purkinje neurons.

Many mammalian cells have a single hair-like structure, known as the primary cilium that projects away from the surface of the cell. This small projection from the membrane regulates many signaling pathways, particularly during embryonic development. However, most of the neurons in the adult brain also have primary cilia, and it is not yet understood what the role of the primary cilium has in maintaining most adult tissues. The primary cilium needs the protein TTBK2 to assemble, and mutations in the gene that codes for this protein cause a neurodegenerative disorder that first appears in adulthood known as spinocerebral ataxia type 11 (SCA11). People with this disease have a movement disorder caused by the loss of neurons called Purkinje cells in the cerebellum. In 2018, researchers showed that mutated versions of TTBK2 associated with SCA11 interfere with the role of normal TTBK2 in assembling the cilium. But it was unclear whether primary cilia are required for the survival of Purkinje cells in the cerebellum. Now, Bowie and Goetz (who are two of the researchers that conducted the 2018 study) have found that deleting the gene that codes for TTBK2 in the brain of adult mice leads to the loss of cilia, followed by impaired movement. Additionally, the connections between Purkinje cells and other neurons are lost, and Purkinje cells eventually degenerate and die. If the cilia are removed using a different mechanism, the results are the same, showing for the first time that primary cilia are important to keep Purkinje cells alive and connected to other neurons. These results shed light on the roles of primary cilia within adult tissues, and provide insight into the mechanisms underlying SCA11, a neurodegenerative disease for which no treatment currently exists. In the future, it will be important to extend the results of this study to other types of neurons affected in different neurodegenerative conditions. Ultimately, this line of research could lead to uncovering the causes of certain neurodegenerative disorders and provide new paths to treatment.