TTBK2T3290C mutation in spinocerebellar ataxia 11 interferes with ciliogenesis

Abstract

This study aimed to elucidate the impact of the TTBK2 T3290C mutation (MUT) associated with Spinocerebellar Ataxia 11 (SCA11) on TTBK2 expression, function, and ciliogenesis. Lymphocytes were isolated from peripheral blood samples of SCA11 family members with the MUT and healthy controls (wild-type, WT). HEK-293 cells transfected with either WT or MUT TTBK2 plasmids were used to assess the MUT’s impact on TTBK2 protein expression, enzymatic activity, and its binding to Cep164 protein. Mouse embryonic fibroblast cells transfected with WT or MUT TTBK2 plasmids examined the MUT’s effect on cilia formation. Clinically, there was no significant difference in the expression of TTBK2 between the SCA11 patients and healthy individuals. The TTBK2 T3290C MUT did not affect protein expression or enzymatic activity but did reduce ciliary formation in embryonic cells and decreased binding affinity to Cep164. Therefore, our data suggested that the TTBK2 T3290C MUT in SCA11 may impair ciliogenesis by weakening the interaction with Cep164.

Keywords

• sca11
• ttbk2
• ciliogenesis
• cep164
• missense mutation