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Professor of Cell Biology Investigator, Howard Hughes Medical Institute |
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Phone: (203) 737-5207 Lab: (203) 737-4453/-4451 Fax: (203) 737-5246 e-mail: susan.ferronovick@yale.edu |
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Department of Cell Biology <Courier Address> |
Vesicle traffic and organelle inheritance
Vesicle Traffic
For our studies on vesicle traffic, we have focused on the multiprotein complex called TRAPP. There are two forms of
the TRAPP complex, TRAPP I and TRAPP II. TRAPP I is required for membrane traffic from the endoplasmic reticulum (ER)
to the Golgi, while TRAPP II is required for traffic between subcompartments of the Golgi.
Interestingly, spondyloepiphyseal dysplasia tardia, a recessive disorder in bone formation is caused by mutations in
the human orthologue of a TRAPP subunit.
Using a vesicle binding assay that employs in vitro formed ER-derived vesicles and pure TRAPP I, we have demonstrated that TRAPP I specifically binds to ER to Golgi vesicles. These findings imply that TRAPP I plays a key role in conferring the specificity of ER to Golgi vesicle traffic. TRAPP I binds to an uncoated ER-derived vesicle through an unidentified ligand (see Figure). Once binding occurs, TRAPP I activates the small GTPase Ypt1p, converting it from its GDP-bound to its GTP-bound form. The activation of Ypt1p by TRAPP I may be the signal that the vesicle has reached its correct acceptor compartment. This then leads to the recruitment of other components, such as Uso1p and the SNAREs. The pairing of the SNAREs, a class of membrane proteins that are required for membrane fusion, is the final step in docking an ER-derived vesicle to the Golgi.
Organelle Inheritance
A model for the role of TRAPP I in tethering ER to Golgi vesicles. Cargo, which buds from the ER, is packaged into coated vesicles (1). The coat is shed (2), exposing the vesicle surface. TRAPP I then interacts with an unidentified element (pink) of the vesicle to tether the vesicle to the cis-Golgi (3). Following TRAPP I-dependent activation of Ypt1p (blue; 4), possible effectors such as Uso1p are recruited to aid in vesicle tethering.
for PDFSacher M, Barrowman J, Wang W, Horecka J, Zhang Y, Pypaert M, Ferro-Novick S. (2001) TRAPP I implicated
in the specificity of tethering in ER-to-Golgi transport. Mol Cell 7: 433-442.
Wang W & Ferro-Novick S. (2002) A Ypt32p exchange factor is a putative effector of Ypt1p. Mol Biol Cell 13:
3336-3343.
Estrada P, Kim J, Coleman J, Walker L, Dunn B, Takizawa P, Novick P, Ferro-Novick S. (2003) Myo4p and She3p are required for cortical ER inheritance in Saccharomyces cerevisiae. J Cell Biol. 163: 1255-1266. [Featured in Comment, Wagner W, Hammer JA 3rd. (2003) Myosin V and the endoplasmic reticulum: the connection grows. J Cell Biol. 163(6):1193-6. (PDF)]
Barrowman J, Wang W, Zhang Y, Ferro-Novick S. (2003) The Yip1p/Yif1p complex is required for the fusion
competence of ER-derived vesicles. J Biol Chem. 278: 19878-19884.
Cai H, Zhang Y, Pypaert M, Walker L, and Ferro-Novick S. (2005) Mutants in trs120 disrupt traffic from the early endosome to the late Golgi. J Cell Biol. 171(5): 823-833.
