Chemical Biology Seminar by Dr. Denisa Jamecna (Biochemie Zentrum Heidelberg / Osnabrück University, Germany)
Event details
| Date | 28.05.2024 |
| Hour | 16:15 › 17:15 |
| Location | |
| Category | Conferences - Seminars |
| Event Language | English |
Title:
STARD3 is involved in sphingosine transport at lysosome-ER contact sites
Abstract:
Sphingolipid transport between organelles has been increasingly studied during the last years and a large body of evidence points to protein-mediated sphingolipid transfer at organelle contact sites. This is well characterized for the transfer of ceramide, glucosylceramide and glycolipids along the sphingolipid biosynthetic pathway from the endoplasmic reticulum (ER) towards the plasma membrane. However, the catabolic pathway is far less studied. Here, a crucial, but unexplored step is the recycling of sphingosine backbone upon lysosomal sphingolipid degradation and its re-integration into the biosynthetic pathway at the ER. In our work, we propose that the lysosomal cholesterol transporter STARD3 may act as a sphingosine transfer protein.
STARD3 has been previously described to tether lysosomes to the ER. At this contact, its START-domain transfers cholesterol from the ER to lysosomes to support endosome maturation. We employed functionalized, photocrosslinkable sphingosine in intact cells to show that STARD3 crosslinks with sphingosine. In addition, in vitro studies confirmed sphingosine binding and molecular dynamic simulations identified that the cholesterol-binding pocket in the START-domain is able to accommodate sphingosine as well. Functionally, we could show that overexpression of STARD3 drives the sphingosine metabolism towards biogenesis of higher sphingolipid species such as sphingomyelin, while depleting cellular Stard3 levels results in a delayed sphingosine metabolism, which indicates STARD3 as a lysosomal sphingosine exporter. This transfer is dependent on a functional FFAT motif, consistent with sphingosine transfer taking place at the lysosome-ER contact site.
Speaker:
Dr. Denisa Jamecna began her academic journey with a BSc in Molecular Biology from Masaryk University in Brno, Czech Republic, completed in 2013. She then pursued a MSc in Neuroscience at University College London, UK, graduating in 2014. Dr. Denisa Jamecna continued her research with a PhD in Biochemistry under the supervision of Dr. B. Antonny at the University of Nice, France, from 2014 to 2018. Following her PhD, she completed two postdoctoral positions: first with Dr. A.-C. Gavin at EMBL Heidelberg, Germany (2019-2020), and then with Dr. D. Höglinger at the Biochemie Zentrum Heidelberg, Germany (2020-2024). In June 2024, Dr. Denisa Jamecna will begin her role as a junior group leader at Osnabrück University in Germany.
STARD3 is involved in sphingosine transport at lysosome-ER contact sites
Abstract:
Sphingolipid transport between organelles has been increasingly studied during the last years and a large body of evidence points to protein-mediated sphingolipid transfer at organelle contact sites. This is well characterized for the transfer of ceramide, glucosylceramide and glycolipids along the sphingolipid biosynthetic pathway from the endoplasmic reticulum (ER) towards the plasma membrane. However, the catabolic pathway is far less studied. Here, a crucial, but unexplored step is the recycling of sphingosine backbone upon lysosomal sphingolipid degradation and its re-integration into the biosynthetic pathway at the ER. In our work, we propose that the lysosomal cholesterol transporter STARD3 may act as a sphingosine transfer protein.
STARD3 has been previously described to tether lysosomes to the ER. At this contact, its START-domain transfers cholesterol from the ER to lysosomes to support endosome maturation. We employed functionalized, photocrosslinkable sphingosine in intact cells to show that STARD3 crosslinks with sphingosine. In addition, in vitro studies confirmed sphingosine binding and molecular dynamic simulations identified that the cholesterol-binding pocket in the START-domain is able to accommodate sphingosine as well. Functionally, we could show that overexpression of STARD3 drives the sphingosine metabolism towards biogenesis of higher sphingolipid species such as sphingomyelin, while depleting cellular Stard3 levels results in a delayed sphingosine metabolism, which indicates STARD3 as a lysosomal sphingosine exporter. This transfer is dependent on a functional FFAT motif, consistent with sphingosine transfer taking place at the lysosome-ER contact site.
Speaker:
Dr. Denisa Jamecna began her academic journey with a BSc in Molecular Biology from Masaryk University in Brno, Czech Republic, completed in 2013. She then pursued a MSc in Neuroscience at University College London, UK, graduating in 2014. Dr. Denisa Jamecna continued her research with a PhD in Biochemistry under the supervision of Dr. B. Antonny at the University of Nice, France, from 2014 to 2018. Following her PhD, she completed two postdoctoral positions: first with Dr. A.-C. Gavin at EMBL Heidelberg, Germany (2019-2020), and then with Dr. D. Höglinger at the Biochemie Zentrum Heidelberg, Germany (2020-2024). In June 2024, Dr. Denisa Jamecna will begin her role as a junior group leader at Osnabrück University in Germany.
Practical information
- Informed public
- Free
Organizer
- Dr. Milena Schuhacher