Home Research Project Details A1 - Transducer adaptation and mechanical stimulus processing in microtubule - based sensory cells
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A1 - Transducer adaptation and mechanical stimulus processing in microtubule - based sensory cells

Martin Göpfert and Christoph Schmidt

Sensory transduction takes place at the input end of most neuronal signal processing. One important subcategory is mechanotransduction. Many mechanosensory cells use specialized organelles for mechanotransduction such as microtubule-based cilia or actin-based hair bundles. The microscopic function of ciliated mechanoreceptors is not well understood [Hudspeth 2008]. The transduction modules in the ciliated mechanoreceptors of the Drosophila hearing organ consist of serially arranged transduction channels and adaptation motors [Albert et al. 2007, Nadrowski et al. 2008]. Nothing is known about their exact location, the way forces are transmitted to these modules, and the identities of the (presumably kinesin- or dynein-type) adaptation motors. To address these issues, we will (a) directly probe the mechanical properties of the sensory cilia with optical traps, (b) narrow down the identities and localization of the motors, and (c) explore their properties in vivo and in vitro. (d) The role of transducer adaptation in mechanical stimulus sorting will be assessed, and experimental data on cellular and molecular properties will be merged into a dynamic model [Nadrowski et al. 2008] to foster a molecules-to-systems understanding of how mechanosensory stimuli are detected and processed.

(a) Based on existing expertise [Albert et al. 2007, Nadrowski et al. 2008, Mizuno et al. 2007, Mizuno et al. 2008, Mizuno et al. 2009], we have established a life-fly preparation that allows us to directly probe the mechanics of individual cilia in the Drosophila hearing organ through the cuticle by means of optical traps and laser interferometry. Using this preparation, the propagation of forces and movements along the cilium and the properties of associated structures such as the rods that surround the cilium will be systematically explored. Experiments will be combined with electrophysiological recordings to link neural activity and ciliary movements and enhancer trap lines will be used to distinguish coexisting sound- and gravity-sensitive cells [Kamikouchi et al. 2009].

(b) Using available mutants and cell type-specific RNAi, we will systematically probe which motor proteins are crucial for transducer adaptation, whereby the function of the adaptation motors will be assayed in vivo by analyzing mechanical correlates of transducer adaptation [Albert et al. 2007, Nadrowski et al. 2008]. If needed, conditional mutants will be made. UAS-fusion constructs and antibodies will be used to determine protein localization, and EM will be used to test for ultrastructural defects.

(c) Motor properties will further be explored in vivo by analyzing mechanical correlates of transducer adaptation [Albert et al. 2007, Nadrowski et al. 2008] and in vitro in standard single-molecule optical trap and single-molecule fluorescence assays and kinetics of motor reactions will be explored [Gittes et al. 1996, Kwok et al. 2006].

(d) Quantitative information about properties of the motors, the cilia, and associated structures will be directly fed into a transducer-based model of the Drosophila hearing organ to analytically and numerically simulate how these properties impact on overall auditory system performance [Nadrowski et al. 2008]. This study will be the first to assess the properties of microtubule-based mechanosensory cells in a sensory organ and to link auditory transduction mechanisms and Drosophila genes. It will help to refine models of fly auditory transduction, provide important general information about the molecular conservation of auditory transduction modules across species [Hudspeth 2008, Albert et al. 2007, Nadrowski et al. 2008], and contribute to our understanding of how intracellular transducer dynamics contributes to the adaptive information processing of mechanical stimulus forces as imposed by sound and gravity/wind.

Belongs to Group(s):
Cell Biophysics, Cellular Neurobiology

Is part of  Section A 

Members working within this Project:
Jähde, Philipp 
Göpfert, Martin 
Schmidt, Christoph 
Prahlad, Achintya 

Selected Publication(s):

Geurten, BR, Jähde, P, Corthals, K, and Göpfert, MC (2014).
Saccadic body turns in walking Drosophila
Frontiers in Behavioral Neuroscience 8(Article 365):1-10.

Soulavie, F, Piepenbrock, D, Thomas, J, Vieillard, J, Duteyrat, J, Cortier, E, Laurencon, A, Göpfert, MC, and Durand, B (2014).
Hemingway is required for sperm flagella assembly and ciliary motility in Drosophila
Molecular Biology of the Cell(25 (8)):1276-86.

Effertz, T, Nadrowski, B, Piepenbrock, D, Albert, JT, and Göpfert, MC (2012).
Direct gating and mechanical integrity of Drosophila auditory transducers require TRPN1
Nature Neuroscience 15(9):1198-1200.

Effertz, T, Wiek, R, and Göpfert, MC (2011).
NompC TRP channel is essential for Drosophila sound-receptor function
Curr Biol 21:592-597.