Young Investigator Research Grant

Michael Stankewich, PhD

Yale School of Medicine
Molecular Mechanisms of Beta 3 Spectrin in Spinocerebellar Ataxia 5 (SCA5)

Spinocerebellar ataxia (SCA) is a dominantly inherited progressive neurodegenerative disorder that results in slurred speech, impaired gait, and loss of coordination. One type, spinocerebellar ataxia type 5 (SCA5) is caused by mutations in the ßIII spectrin gene as reported in Abraham Lincoln’ s family lineage as well as in two other European families. Other examples of spectrin dysfunction in ataxia rodent models include the transgenic SCA1 and staggerer mice, ß?V spectrin mutations in the quivering mice, and ankyrin R and ankyrin G gene knockout mice. Given that the spectrin/ankyrin cytoskeleton is required for the organization of a diverse set of membrane proteins, including ion channels, receptors, and cell adhesion molecules, one emerging paradigm for ataxia pathogenesis follows. This paradigm is dissolution of the spectrin/ankyrin cytoskeleton, which causes a failure in the cellular localization of certain membrane proteins resulting in the loss of their physiological function, can cause ataxia.