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Jeff Gerst
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| Tel. | 08-934 2106 |
| Fax. | 08-934 4108 |
| Location | Room 411 Arthur and Rochelle Belfer Building for Biomedical Research, Weizmann Institute of Science, Rehovot 76100, Israel |
| Jeffrey.Gerst@weizmann.ac.il | |
|
Jeff Gerst
|
| Tel. | 08-934 2106 |
| Fax. | 08-934 4108 |
| Location | Room 411 Arthur and Rochelle Belfer Building for Biomedical Research, Weizmann Institute of Science, Rehovot 76100, Israel |
| Jeffrey.Gerst@weizmann.ac.il | |
Polarized growth is essential for a variety of cellular processes, including: cell division, differentiation, motility, and tissue formation. The establishment of cell polarity in eukaryotes involves asymmetric organization of both the actin cytoskeleton and secretory pathway to lead to the polarized distribution of new membrane along a given axis. We study the molecular requirements necessary for the transport of newly synthesized proteins and lipids to the cell surface, via secretory vesicles, as well as the role of mRNA transport and localization in the establishment and maintenance of this process.
As simple and complex organisms utilize similar strategies to deliver proteins and lipids to the cell surface, we use the yeast, Saccharomyces cerevisiae, as a model system in which to study intracellular transport. Because yeast are genetically tractable, it allows us to identify genes that facilitate protein and mRNA transport in a simple and rapid fashion. Our work can be divided into three major subjects: 1) SNARE regulation and vesicle transport; 2) endosomal protein sorting and human disease; and 3) mRNA transport and protein localization.
First, we are studying the connection between cell signaling pathways and the control of membrane fusion. We have shown that SNAREs, which are conserved membrane fusogens, are modified post-translationally by kinases involved in cell cycle and growth control. SNARE phosphorylation regulates protein transport at the levels of exo- and endocytosis [1,3,5], as well as transport through the Golgi [8]. Ongoing work seeks to reveal the mechanism by which phosphorylation and dephosphorylation control SNARE functions throughout the secretory pathway. We are also examining the molecular requirements necessary for secretory vesicle biogenesis and delivery to the cell surface. Our work suggests a more direct role for endosomal sorting compartments in the delivery of proteins and lipids to the cell surface [2], and that the delivery of phosphoinositides to the cell surface regulates the actin cytoskeleton and polarized growth [17,19].
Second, we are studying the mechanisms of endosomal protein sorting and delivery to the vacuole/lysosome [10-12,16]. In particular, we use yeast as a model for Batten Disease, a severe neurodegenerative disorder that results from the aberrant accumulation of material in lysosomes. Our work suggests that mutations in the yeast orthologs of human Batten disease genes have specific defects in endosomal trafficking steps [12]. Thus, yeast can serve as a simple tool to understand how Batten disease and related human lysosomal storage disorders occur.
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| GFP-Yif1 (green fluorescence), a Golgi marker, is mislocalized to the vacuole (red fluorescence) in the absence of the BTN2 Batten disease-related gene |
Third, we are examining the role of mRNA transport in the control of secretion and cell growth, and our work has shown that mRNAs encoding polarity and secretion factors are targeted along with cortical ER to the site of polarization [13]. mRNA-ER co-transport appears to have been conserved in evolution and allows for the local translation of proteins distal to the cell soma [15]. In addition, we have developed novel methods to visualize endogenous mRNAs in living cells for the first time [14,18] and are examining whether all mRNAs are targeted to specific intracellular locations. By employing systematic gene-tagging studies, we are examining the localization of mRNAs encoding proteins of the peroxisome [20], mitochondria, actin cytoskeleton, autophagosome, as well as other intracellular organelles and structures. The results suggest that most, if not all, mRNAs are targeted within the cell to discrete destinations, probably to allow for the correct placement of the newly translated protein.
PEX14 mRNA (green fluorescence), which encodes a peroxisomal protein, associates with peroxisomes (red fluorescence) throughout the cell cycle
Updated: 23/12/2009 14:36:45 Contact E-mail: Jeff.Gerst@weizmann.ac.il