Publications
Research Projects
The oxytocin receptor and its dependence on cholesterol
Oxytocin is a neurohypophyseal nonapeptide that can induce several physiological (peripheral and central) responses. Among the best-known peripheral effects of oxytocin are the contraction of smooth muscles in the myometrium (labor inducing) and myoepithelial cells of the mammary gland (lactation). One special property of the oxytocin receptor refers to its dependence on cholesterol. The high-affinity state of the oxytocin receptor requires the presence of a high cholesterol environment. Cholesterol also has a stabilizing function for the receptor. We have therefore proposed that one or more cholesterol molecules directly interact with the oxytocin receptor. In 2020, the first crystal structure of the receptor was published (Waltenspühl et al., 2020 in Sci Adv 15:eabb5419) and has confirmed the presence of a specific cholesterol binding site within the oxytocin receptor. A cholesterol molecule was located between the transmembrane helices IV and V of the receptor.
Recent studies propose that many other GPCRs of the rhodopsin class are also associated with cholesterol. Thus, the oxytocin receptor may be a prototype of a much larger group of receptors that function in close association with cholesterol.
Synthesis of fluorescent cholesterol analogues
Cholesterol is a multifunctional lipid and main structural component of the plasma membrane of higher eucaryotic cells. The intracellular cholesterol concentration is tightly regulated by feedback controls. However, despite much efforts, the transport pathways of cholesterol in the cell are ill-defined. To study the cellular trafficking of cholesterol, we have synthesized novel fluorescent cholesterol analogues. Among these analogues 6-Dansylcholestanol (DChol) was found to be the most appropriate. In CHO cells, we could demonstrate that DChol is esterified with the same kinetics as compared with tritiated cholesterol (Wiegand et al., 2003). DChol applied in form of water soluble cyclodextrin inclusion complexes translocated from the plasma membrane to the endoplasmic reticulum (ER)/Golgi in an energy-independent manner. The kinetics of this transport process was cell-type dependent. Finally, DChol is esterified by acyl-CoA cholesterol acyltransferase (ACAT), an enzyme localized in the ER, and is stored in lipid droplets. The in vivo dynamics of the cholesterol transport and the biogenesis of lipid droplets are studied.
Technical assistant:
Andrea Schiffmann
Coworkers:
Christian Frey (Master thesis, 2022)
Cristiano Schettino (Bachelor, 2020)
Larisa Cristea (Bachelor, 2020)
Muna Mustafa (Diploma thesis, 2019)
Sarah König (Diploma thesis, 2019)
Yvonne Jakob (Diploma thesis, 2018)
Halima Freund (Master thesis, 2018)
Sandra Libera (Master thesis, 2017)
Larissa Bessler (Bachelor, 2016)
Lena Ahlswede (Master thesis, 2016)
Lisa Hueske (Bachelor, 2015)
Sandra Libera (Bachelor, 2015)
Elena Steiert (Bachelor, 2014)
Patricia Rostan (Bachelor, 2014)
Adeline Haag (Diploma thesis, 2014)
Michaela Christmann (Diploma thesis, 2013)
Richard Weber (Bachelor, 2013)
Katharina Kern (Bachelor, 2013)
Christina Behrendt (Diploma thesis, 2013)
Olivia Bauer (Diploma thesis, 2012)
Ulrike Kintzel (Bachelor, 2012)
Özlem Kilic (Staatsexamen thesis, 2011)
Alexander Maiwald (Diploma thesis, 2011)
Rebecca Hamm (Diploma thesis, 2010/1011)
Anja Fries (Diploma thesis, 2009)
Barbara Knapp (Diploma thesis, 2009)
Conny Trossen (Diploma thesis, 2003, PhD student)
Sabine Muth (Brauer) (Diploma thesis, 2008)
Ulla Faust (Diploma thesis, 2008)
Anne Crombe (Diploma thesis, 2007)
Svetlana Usanova (Diploma thesis, 2005)
Volker Wiegand (PhD thesis, 2002)
Julian Reitz (PhD thesis, 2001)