A23 - Characterization of the membrane scaffold complexes that tune photoreceptor neuron function

Principal Investigator

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.

Figure Caption: How do membrane scaffolds shape modality-specific photoreceptor properties?

Membrane scaffolds shape the function of insect photoreceptor cells (center) at multiple levels, shown on the Left and Right side, respectively.

Left side: The regulation of rhabdomere diameter and its fine structure (regulation of rhabdomeric twist through which polarization sensitive can be destroyed) is essential for producing polarization-sensitive photoreceptors in the ‘dorsal rim area’ of insect eyes (shown for Drosophila in pink, top left). Only in these DRA ommatidia, rhabdomeres of R7 and R8 cells (located on top of each other) both express the UV Rhodopsin 3 (rh3), are untwisted and oriented orthogonally (top right). A sharp boundary exists between DRA ommatidia and non-DRA ommatidia (shown with Anti-Homothorax expression in DRA R7 and R8 (center left), as well as serial reconstruction of photoreceptor rhabdomere twist (R7: red vs R8: blue; all bottom left).

Right side:  Anchoring of Rhodopsin molecules within the phototransduction scaffold of rhabdomeric microvilli is essential for high polarization sensitivity. Linearly polarized skylight forms a pattern around the sun which can be exploited by many animals for improving their navigational skills (left). As it hits untwisted rhabdomeric microvilli of polarization-sensitive insect photoreceptors, straightly aligned Rhodopsin molecules preferentially absorb light vibrating in one particular plane (symbolized by double-headed arrows, right). Although the mechanism for the anchoring of Rhodopsin molecules within the rhabdomeric microvilli remains unknown, the membrane scaffold formed by the phototransduction machinery serves as a likely candidate.

[Center schematic modified from Chang and Ready, 2000; Pictures from Wernet et al, 2003; Wernet et al, 2012; Wehner, 1976; Homberg, 2005; Hardie & Juusola, 2015].


  1. Wernet, M.F., Labhart, T., Baumann, F., Mazzoni, E.O., Pichaud, F., and Desplan, C. (2003) Homothorax switches function of Drosophila photoreceptors from color to polarized light sensors. Cell 115(3):267-79.
  2. Mikeladze-Dvali, T.*, Wernet, M.F.*, Pistillo, D., Teleman, A., Chen, Y.W., Mazzoni, E.O., Desplan, C. (2005). The growth regulators Dlats and Melted interact in a bistable loop to specify opposite fates in R8 photoreceptors. Cell 122(5):775-87. *equal contribution.
  3. Wernet, M.F.*, Mazzoni, E.O.*, Celik, A.*, Duncan, D.A., Duncan, I., Desplan, C. (2006). Stochastic expression of the Drosophila Dioxin receptor Spineless creates the retinal mosaic required for color vision. Nature 440(7081):174-80. *equal contribution.
  4. Wernet, M.F., Celik, A., Mikeladze-Dvali, T., Desplan, C. (2007). Generation of uniform fly retinas. Current Biology 17(23):R1002-3.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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