Anne SpangDivision of Biochemistry, University of Basel, Basel, Switzerland F1000 Faculty Member (since 04 July 2001)
Since 2005 Professor at the Biozentrum
Transport between different cellular compartments is achieved by vesicular traffic. Three major coats involved in vesicle formation have been identified to date. Clathrin is involved in transport between the trans-Golgi network and the plasma membrane. COPII mediates transport from the endoplasmic reticulum to the Golgi. Finally, COPI-coated vesicles are involved in a number of transport steps, mainly forward transport from the ER to the Golgi, possibly intra-Golgi transport, and retrograde transport from the late Golgi compartments to earlier compartments and back to the ER. The different destinations of various COPI-coated vesicles raise the question how transport is regulated. One layer of regulation and specificity comes definitely from the SNAREs, which are present on both the target membranes (t-SNAREs) and on the vesicles (v-SNAREs). However, it has been shown that v-SNAREs cycle between different compartments; thus other factors, which confer specificity to vesicle targeting and fusion, must be involved. We are interested in studying the mechanisms underlying cargo recruitment into vesicles, vesicle formation, and vesicle targeting. Our efforts are concentrated on elucidating the regulation of COPI-vesicles that bud from the Golgi and are destined to the ER using the yeast Saccharomyces cerevisiae as a model system.
Cytosolic Arf1p is inactive and has bound GDP (Arf1p-GDP). Upon interaction with a guanine nucleotide exchange factor (Arf1-GEF), the now activated Arf1p-GTP binds to the membrane. At the Golgi membrane, Arf1p-GTP interacts with a GTPase activating protein (Arf1-GAP) and might help recruiting not only coatomer (with which Arf1p forms the COPI-coat) but also cargo molecules into COPI-coated vesicles. The COPI-vesicle then buds off the Golgi membrane. The COPI-coat is turned over which results in uncoating of the vesicle. The vesicle is then able to fuse with an acceptor compartment (in our case the ER) and the soluble components of the COPI coat can undergo another round of transport.
We are still far away from understanding membrane traffic. Therefore, the current research will keep us busy also in the future. However, we want to embark also in another direction: understanding asymmetric cell division in the nematode C. elegans.
Beyond the cleavage furrow - cytokinesis in C. elegans
Cell division is one of the most important events in the life of a cell. A cell needs to replicate the DNA, divide it equally between two poles during mitosis and finally the cleavage furrow separates mother and daughter cell giving raise to 2 cells. This last event is called cytokinesis. We use the nematode Caenorhabditis elegans as a model organism to study cytokinesis. We focus on the transport of membranes into the division plane and the insertion into the ingressing cleavage furrow. In order to tackle these problems, we use RNAi approaches and perform genetic screens. This will result in the identification of key players for the formation of the cleavage furrow during cytokinesis. So far we succeeded in identifying some genes, that are currently under investigation in our lab. However the long-term goal is to use cell biology and biochemistry to recapitulate cytokinesis.
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