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Mischievous meaning10/31/2023 In the new study, the researchers focused on four mutations that are linked to autism or other neurodevelopmental conditions and that prevent TAOK1 from phosphorylating its targets. But how TAOK1 mutations trigger connectivity changes was unclear. Turning up TAOK1 gene levels in mice distorts dendritic spines, and depleting the invertebrate version of the protein in fruit flies leads to overgrown dendrites and hyperconnectivity. Previous studies hinted at TAOK1’s potential role in neuronal wiring. “But our work shows that they are very different proteins, doing very different things.” “When people talk about TAOKs, they kind of lump them altogether and think of them as doing the same thing,” says lead investigator Smita Yadav, assistant professor of pharmacology at the University of Washington in Seattle. For instance, TAOK2, located on a chunk of chromosome 16 that is missing in some autistic people, regulates neuronal migration. All three enzymes contribute to brain development, and mutations that disrupt their function have been linked to autism in earlier work. The gene belongs to a family of three TAO kinases that add phosphate groups to signaling proteins. Those irregularities could contribute to core traits associated with TAOK1 mutations, such as intellectual disability. TAOK1, a gene strongly linked to autism and other neurodevelopmental conditions, helps to mold the membrane, and mutations in the gene deform the neuronal surface, a new study shows. It continually shifts its shape, bulging outward to sprout antenna that guide cell movement or branches that connect with other neurons, in a process orchestrated by membrane-remodeling proteins. The neuronal membrane is a dynamic place.
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