Dr. Nava Segev
- PhD, Tel Aviv University, Israel
- Postdoctoral Research MIT, Cambridge MA (Advisor: David Botstein)
Research Interests: Regulation of Intracellular Trafficking by Molecular Switches and Cascades:
The Role of Ypt/Rab GTPases
Regulation of Intracellular Trafficking by Molecular Switches and Cascades
Our research is aimed at understanding a basic cellular process, trafficking inside cells, in which proteins and membranes are shuttled between cellular organelles. This process is required for proper functioning of all cells, and therefore for every system of the human body. Elucidation of the mechanisms that regulate trafficking inside cells is relevant to a variety of diseases caused by impaired transport of substances that are either essential, such as insulin in diabetes, growth-factor receptors in cancer and CFTR in cystic fibrosis, or detrimental, such as -amyloid in Alzheimer’s disease.
The conserved molecular switches Ypt (in yeast) and Rab (in humans) GTPases have emerged as key regulators of individual transport steps. They are activated by guanine-nucleotide exchange factors (GEFs), and when in the active form, they interact with downstream effectors that mediate vesicular transport. Our long-term goal is to elucidate how Ypt/Rab GTPases together with their GEFs and effectors coordinate multiple transport steps and pathways.
To address these complicated issues, we are using yeast as a model because it allows utilizing sophisticated genetic approaches in combination with molecular and cellular methods. Furthermore, the relatively small number of players (e.g., 11 Ypts in yeast versus ~70 Rabs in humans) and the resultant simplified interaction networks make yeast an excellent model for studying the coordination of transport steps. Currently, we are studying the role of Ypt GTPases in secretion and in the cellular recycling pathway autophagy.
Regulation of Golgi Cisternal Progression by Ypt/Rab GTPases. Kim JJ, Lipatova Z, Majumdar U, Segev N. Dev Cell. 2016 Feb 22;36(4):440-52
.A Role for Macro-ER-Phagy in ER Quality Control. Lipatova Z, Segev N. PLoS Genet. 2015 Jul 16;11(7):e1005390.
Regulation of selective autophagy onset by a Ypt/Rab GTPase module. Lipatova Z, Belogortseva N, Zhang XQ, Kim J, Taussig D, Segev N. Proc Natl AcadSci U S A. 2012 May 1;109(18):6981-6.
Coordination of intracellular transport steps by GTPases. Segev N.Semin Cell Dev Biol. 2011 Feb;22(1):33-8. doi: 10.1016/j.semcdb.2010.11.005. Epub 2010 Dec 2. Review.
Trafficking Inside Cells: Pathways, Mechanisms and Regulation Segev, N., Editor (2009) Publisher: Springer Science + Business Media.
Rab GTPases and Membrane Trafficking Guangpu Li, Nava Segev, Editors (2012) Publisher: Bentham Science