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Golgi apparatusThe Golgi apparatus, shown here in an illustration, has a famous stack-of-pancakes structure that is caused by three molecules pulling on its edges, according to new research.djgunner/iStockphoto

Researchers have pinpointed a protein that keeps the trains running through the cell’s Grand Central station.

The protein works in tandem with other molecules to pull membrane packets off the surface of a cell’s Golgi apparatus, giving the crucial organelle its distinctive flattened shape.

“It’s a nice simple mechanism for how the shape of something is a consequence of its function,” says Seth Field of the University of California, San Diego and a coauthor of the study, which appears in the Oct. 16 Cell. “It’s a lot simpler than people would have guessed.”

The Golgi apparatus is the staging area for all proteins whose final destinations lie outside the cell, including hormones, antibodies and components of hair, bone and skin. Everything that is needed elsewhere in the body goes through the Golgi to get packaged and prepared for its journey. The proteins leave the Golgi wrapped in vesicles, bubbles of the organelle’s membrane.

The function of the Golgi apparatus is well known, but its odd shape has long been a mystery. Researchers have described it as a stack of pancakes or a pile of deflated balloons. The pancakes are membranes that enclose empty space that proteins travel through.  

“No one had understood why the Golgi looks like that, what purpose that serves,” Field says.

Now Field and his colleagues have pinpointed the protein responsible. In an analysis of the binding properties of 4,000 fruit-fly proteins, one called GOLPH3 latched onto another molecule that was known to be important to the Golgi’s function.

Further scans found that a motor protein like those found in muscles also piggybacked on GOLPH3. The researchers found that if any one of these three molecules — GOLPH3, the molecule it attached to or the motor protein — was removed, the Golgi apparatus structure collapsed.

“Instead of being flattened pancakes, they’re rounded up, like balls of dough,” Field says.

The removal also shut down the Golgi’s function. Proteins meant to travel through the Golgi apparatus and out of the cell never made it. The trains never reached their destinations.

The team concluded that the organelle’s stretchy shape is a side effect of its job. The motor protein enables GOLPH3 to pull bubbles full of proteins off the Golgi apparatus and send them outside the cell. In the process, the membranes are pulled flat, like rubber bands.

“It immediately suggests a very elegant answer to a few aspects of why the Golgi looks the way it does,” Field says.

Surprisingly, GOLPH3 has also been implicated in cancer formation. A paper in the June 25 Nature found that the protein shows up in droves in a large fraction of human tumors.

“We don’t really understand why a protein at the Golgi, when overexpressed, might cause cancer, but clearly it does,” Field says. “That’s one thing we’re working on now, to figure out what the connection is.”

“This is a very novel and interesting paper,” says Helen Yin of the University of Texas Southwestern Medical Center at Dallas. Linking the three molecules as crucial to the Golgi apparatus “ties together a lot of things that people have suspected but couldn’t quite put their hands on.” The cancer connection is incredibly interesting, she adds. “If there is a link to cancer, that will take off” as a new research direction.

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