Proteins are transported to specific sites within cells enclosed in packets
called transport vesicles, along a specialized network of tracks called
microtubules. Transport vesicles are targeted to the correct acceptor membrane
by a number of sequential steps that are regulated by small GTPases of the Rab
and Arf families. The initial interaction between vesicles and the target
membrane is thought to be mediated by very large molecular "tethers" that link
the two membranes prior to fusion. A Stanford team from the Brunger and
Pfeffer laboratories has studied how one such putative tether molecule is
localized to the membranes of an organelle called the Golgi complex.
The work shows that binding of 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 membrane-attached GTPases provide
stable binding of the tether to the Golgi complex.
Using x-ray diffraction data collected at SSRL, researchers Alondra Schweizer
Burguete and Timothy Fenn determined the structure of a region of the tether in
complex with the Rab6 GTPase. They created a model of the system to visualize
how the GTPases might cooperate to anchor the tether and thereby capture
incoming vesicles. In this model, proteins belonging to the Rab and Arf GTPase
families reside at the membrane-anchor point of the tether. A pair of Arl1
GTPase molecules form a previously characterized complex with the tether close
to the membrane. At a significant distance (10 nanometers) away from the
membrane, a pair of Rab6 molecules bind a distinct tether-region; the Rab
GTPases are able to reach this far thanks to their extended and unstructured
tail-domains.
The model explains how Arl1 and Rab6 GTPases may cooperate in anchoring the
tether to the Golgi membrane, thereby 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.
The results are published in the January 25 edition of the journal Cell.
Schweizer Burguete, A., Fenn T. D., Brunger, A. T. and Pfeffer, S. R. (2008).
Rab and Arl GTPase Family Members Cooperate in the Localization of the Golgin
GCC185. Cell 132(2), 286-298.
To learn more about this research see the full scientific highlight at:
http://www-
ssrl.slac.stanford.edu/research/highlights_archive/rab-arl_gtpases.html