Prof. Dr. Mathias Wernet, FU Berlin
Scaffold protein complexes define numerous functional properties of neurons. We are interested in how membrane scaffolds specifically tune the functional properties of a photoreceptor cell type through reorganization of its photosensitive membrane morphology, and receptor protein localization.
In the Drosophila eye, different types of photoreceptor neurons located in separate regions express different Rhodopsin receptors to sense light and exert modality-specific functions, e.g. colour vision or polarization vision. We and others have previously shown that a photoreceptor subtype from the 'dorsal rim area' (DRA) is specialized to detect polarized skylight. This modality-specific function is defined by the specialized morphology of light-gathering membranes (rhabdomeres), as well as Rhodopsin localization within the rhabdomeric membranes. However, very little is known on a molecular level, about how these photoreceptors acquire the characteristic morphology that defines their polarization sensitivity. For instance, specific membrane proteins serve as a binding partners for membrane scaffolds regulating multiple aspects of rhabdomere morphogenesis, like the development of apico-basal polarity, directed protein transport, and growth. However, nothing is known about how these processes become differentially regulated in a cell type specific manner. On the other hand, different scaffold proteins are crucial for positioning the Rhodopsin molecule inside the rhabdomere membrane, thereby linking it to its phototransduction components.
We have previously developed genetic methods for the specific manipulation of polarization-sensitive photoreceptors. We use such manipulations to elucidate how membrane scaffolds become re-organized in modality-specific photoreceptors. We are particular interested in the question how membrane scaffolds modulate the DRA- specific rhabdomere morphology like in enlarged diameter and fine structure (twist), both of which are crucial for polarization-sensitivity. Furthermore, we investigate the scaffold interactions necessary for anchoring the Rhodopsin molecules inside the rhabdomeric microvilli of polarization-sensitive photoreceptors. Our approach combines molecular tools and biochemical interaction assays with functional studies (physiology, imaging and behavior). Hence, this approach allows to combine the analysis of scaffold proteins and their interactions required at a subcellular level with the functional outcome at the cellular and organismal level. Taken together, these experiments will reveal the molecular composition of membrane scaffolds that shape functionally specialized photoreceptors.
- Wernet, M.F., Celik, A., Mikeladze-Dvali, T., Desplan, C. (2007). Generation of uniform fly retinas. Current Biology 17(23):R1002-3.
- Wernet, M.F., Velez, M.M., Clark, D.A., Baumann-Klausener, F., Brown, J.R., Labhart, T., Clandinin, T.R. (2012). Genetic dissection reveals two separate retinal substrates for polarization vision in Drosophila. Current Biology 22:1-9.
- Wernet, M.F., Desplan, C. (2014). Homothorax and Extradenticle alter the transcription factor network in Drosophila ommatidia at the dorsal rim of the retina. Development 141(4):918-28.
- Wernet, M.F., Meier, K.M., Baumann-Klausener, F., Dorfman, R., Weihe, U., Labhart, T., Desplan, C. (2014). Genetic dissection of photoreceptor subtype specification by the Drosophila zinc finger proteins Elbow and No ocelli. PLoS Genetics 10(3):e1004210.
- Velez, M.M., Gohl, D., Clandinin, T.R., Wernet, M.F. (2014). Differences in neural circuitry guiding behavioral responses to polarized light presented to either the dorsal or ventral retina in Drosophila. J Neurogenetics 10:1-30.
- Wernet, M.F., Perry, M.W., Desplan, C. (2015). The vast evolutionary diversity of insect retinal mosaics: common design principles and emerging molecular logic. Trends in Genetics. 31(6):316-328.
- Mathejczyk, T.F., Wernet, M.F. (2017). Sensing polarized light in insects. In: Encyclopedia of Neuroscience, Oxford Academy Press. Online publication Sep 17th, 2017. DOI: 10.1093/acrefore/9780190264086.013.10