Multiple axons and actions with PSD-95

Dec 15, 2008
More PSD-95 means bigger spines (top), and multiple axon connections. Credit: Nikonenko, I., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200805132.

Nitric oxide gets neurons together. And it seems to do it backward. Work by Nikonenko et al. suggests that a protein called PSD-95 prompts nitric oxide release from postsynaptic dendritic spines, prompting nearby presynaptic axons to lock on, and develop new synapses. The study will appear in the December 15, 2008 issue of The Journal of Cell Biology (JCB).

It is becoming increasingly clear that synaptogenesis is not solely axon driven. PSD-95 is a major component of postsynaptic densities—a conglomeration of scaffolding proteins, neurotransmitter receptors, and signaling proteins that are thought to shape dendritic spines—and reduced levels of PSD-95 impair synapse development. How PSD-95 works, however, was unknown.

Nikonenko et al. overexpressed PSD-95 in cultured hippocampal neurons and found that the cells' dendritic spines grew two to three times their normal size and were often contacted by multiple axons—a rare occurrence in the adult brain. By mutating different parts of PSD-95, the team discovered that the region responsible for prompting multi-axon connections was also required for binding nitrogen oxide synthase.

The team cut to the chase, bathed neurons in nitric oxide, and showed this was sufficient to promote the extra axon connections. Since bathing cells in nitric oxide and overexpressing proteins do not reflect normal physiological conditions, the team also inhibited nitric oxide synthase in wild-type neurons and confirmed that synapse density was reduced.

Overexpressing PSD-95 increased the amount of nitric oxide synthase at postsynaptic densities, suggesting PSD-95 recruits the synthase to its required locale. Interestingly, PSD-95 that lacked its synthase interaction domain still induced super-sized dendritic spines, suggesting PSD-95 wears more than one hat at the synapse construction site.

More info: Nikonenko, I., et al. 2008. J. Cell Biol. doi:10.1083/jcb.200805132. www.jcb.org

Source: Rockefeller University

Explore further: Birds 'weigh' peanuts and choose heavier ones

Related Stories

NSA winds down once-secret phone-records collection program

58 minutes ago

The National Security Agency has begun winding down its collection and storage of American phone records after the Senate failed to agree on a path forward to change or extend the once-secret program ahead of its expiration ...

Pipeline that leaked wasn't equipped with auto shut-off

1 hour ago

The pipeline that leaked thousands of gallons of oil on the California coast was the only pipe of its kind in the county not required to have an automatic shut-off valve because of a court fight nearly three ...

Uber drivers fined in Hungary

1 hour ago

The Hungarian tax authority fined Uber drivers in its first probe against the ride-sharing service which the economy ministry said Saturday "ignores passenger safety" and must be made to follow regulations.

Recommended for you

Birds 'weigh' peanuts and choose heavier ones

May 23, 2015

Many animals feed on seeds, acorns or nuts. The common feature of these are that they have shells and there is no direct way to know what's inside. How do the animals know how much and what quality of food ...

Q&A: Why are antibiotics used in livestock?

May 22, 2015

Wal-Mart, the world's biggest retailer, is the latest company to ask its suppliers to curb the use of antibiotics in farm animals. Here's a rundown of what's driving the decision: ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.