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Stanford Collaboration Reveals a Case of Microscopic Teamwork

(Photo - Group Photo)The exchange of ideas and information among scientists is nothing new. Now, in fitting parallel, a collaboration between two Stanford labs has revealed a unique case of collaboration in the microscopic world. The results are published in the January 25 edition of the journal Cell.

The GTPase proteins are a large family of enzymes involved in a host of activities inside cells. Using X-ray diffraction at the Stanford Synchrotron Radiation Laboratory (SSRL) beamlines 11-1 and 7-1, researchers from the labs of Stanford professors Axel Brunger and Suzanne Pfeffer have found an unexpected instance of two different GTPase proteins working together. Brunger, whose primary focus is the mechanics of neurotransmission, and Pfeffer, who studies how receptors are moved around in mammalian cells, joined forces to look at how two different GTPase proteins function at the membrane surface of a cellular organelle called the Golgi complex.

Proteins are transported to specific sites within cells enclosed in packets called transport vesicles, which are moved along a specialized network of tracks called microtubules. The Golgi complex is a central sorting station in cells, and is at the center of the cell's secretion machinery. But exactly how vesicles carrying incoming proteins recognize the Golgi as their correct targets is poorly understood.

"Cellular trafficking is important for just about everything in the cell," said Alondra Schweizer Burguete, who led the study. "We know the least about how vesicles recognize their targets. Of all the vesicle transport steps this is least defined." Together with Timothy Fenn, Burguete, who previously worked in the Pfeffer lab and now conducts postdoctoral research in the Brunger lab, bridges the strengths of the two labs on the current research.

Burguete and her colleagues determined the structure of part of a tethering protein in complex with a pair of GTPase proteins called Rab6. They showed that anchoring the tethering protein to the Golgi requires cooperation between two families of GTPases: the Rab family and the Arl family. Only together could the two GTPases provide stable binding of the tether to the Golgi complex.

Having determined the structure of Rab6 in complex with the tether, the team then combined that information with the previously studied Arl1 structure to create a model of the system. The model explains how the Arl1 and Rab6 GTPase pairs may cooperate with each other in directing incoming vesicles to the Golgi membrane prior to fusion. This represents a first-ever instance of such a cooperative relationship among different members of these GTPase families.

"I think what's exciting about our finding is the sort of crosstalk between different G proteins, in this case by having a common binding partner," said Brunger. "This is one of the first examples where we have shown that they interact cooperatively."

"Stanford is a wonderful place because the environment fosters interactions between research groups, departments, with SLAC and across the University," said Pfeffer. "It's a very collaborative and interactive research environment."

—Brad Plummer, SLAC Today, January 28, 2008

Top image: (From left) Axel Brunger, Suzanne Pfeffer, Alondra Schweizer Burguete and Timothy Fenn solved the structure of a Rab6-tether complex, important for transport of proteins within cells.

Lower image: Model of a tether-GTPase complex as viewed from the membrane. The tether (in green) is expected to assume a rod-like shape and extend 100 nm from the membrane, where it would connect to microtubule tracks.


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