autism, protein, brain development
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A protein whose mutations are found in people with autism and other neurodevelopmental conditions helps keep connections between neurons in the brain running smoothly.
Newly published research — led by Rockefeller University in New York City, NY — reveals that the protein astrotactin 2 (ASTN2) can traffick receptors away from neurons’ surfaces and prevent them from accumulating there.

Connections between neurons are essential to brain function.

They work because receptors, which sit on the surfaces of cells, are always ready to partner with incoming neurotransmitters from other cells.

The process is dynamic and needs a continual cycle of receptors “on and off” the cell membrane to ensure rapid response to signals. Trafficking proteins help keep the receptors moving.

The recent study, which now features in the Proceedings of the National Academy of Sciences, has also suggested a mechanism through which autism spectrum disorders (ASDs), such as the neurodevelopmental condition autism, could arise from defects in ASTN2.

The exact causes of neurodevelopmental conditions are largely unknown, though many signs can be traced to early brain development. Scientists believe that the origins are complex and involve genetic, biological, and environmental factors.

According to the Centers for Disease Control and Prevention (CDC), around 1 in 68 children from the United States have been “identified with ASD,” with boys over four times more likely be identified with it than girls.

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Trafficking proteins

In previous work, senior study author Mary E. Hatten, a professor in neurosciences and behavior at the Rockefeller University, had already found that ASTN2 has a trafficking role during early development when cells migrate.

The presence of this protein in the adult brain, however, led lead study author Hourinaz Behesti, when she joined Prof. Hatten’s laboratory, to posit that ASTN2 may also have another role.
Levels of ASTN2 seem to be particularly high in a brain region called the cerebellum. Traditionally, this brain region was thought to concern control of movement, but, report the authors, “recent evidence has suggested” that it may also be involved with “nonmotor functions, including language, visuospatial memory, attention, and emotion.”

Using an electron microscope, the investigators then identified sites of ASTN2 expression in the cerebellums of mice.

They discovered that the protein was mainly to be found in structures called “endocytic and autophagocytic vesicles,” which transport proteins inside neurons.

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