Andreas Rennhack

Center of Advanced European Studies and Research | CAESAR · Department of Molecular Sensory Systems

Cilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca2+ rise that controls motility. The mechanisms underlying such ultra-sensitivity are ill-defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory...

Background and purpose: Sperm from many species share the sperm-specific Ca2+ channel CatSper (cation channel of sperm) that controls the intracellular Ca2+ concentration and, thereby, the swimming behaviour. A growing body of evidence suggests that the mechanisms controlling CatSper activity and the role of the channel during fertilization differ...

Grant: This work was supported by German Research Foundation Grants CRU326 (to T.S. and F.T.) and SFB1089 (to U.B.K.); Cells-in- Motion Cluster of Excellence (Münster) Grant CiM20027 (to T.S.); and a research fellowship from the European Society for Paediatric Endocrinology (to I.V.W.).

The voltage-gated proton channel Hv1 is expressed in various human cell types, including macrophages, epithelial cells, and sperm. Hv1 opening leads to proton efflux that alkalizes the cytosol. Here, we describe light-activated Hv1 inhibitors (photoswitches) that allow controlling its activity with high spatiotemporal precision. The photoswitches c...

The lysosomal acid beta-glucosidase GBA1 and the non-lysosomal beta-glucosidase GBA2 degrade glucosylceramide (GlcCer) to glucose and ceramide in different cellular compartments. Loss of GBA2 activity and the resulting accumulation of GlcCer results in male infertility, whereas mutations in the GBA1 gene and loss of GBA1 activity cause the lipid-st...

Unlabelled: Dendritic voltage-gated ion channels profoundly shape the integrative properties of neuronal dendrites. In epilepsy, numerous changes in dendritic ion channels have been described, all of them due to either their altered transcription or phosphorylation. In pilocarpine-treated chronically epileptic rats, we describe a novel mechanism t...

Sperm require a sense of direction to locate the egg for fertilization. They follow gradients of chemical and physical cues provided by the egg or the oviduct. However, the principles underlying three-dimensional (3D) navigation in chemical landscapes are unknown. Here using holographic microscopy and optochemical techniques, we track sea urchin sp...

Supramolecular self-assembly of amyloidogenic peptides is closely associated with numerous pathological conditions. For instance, Alzheimer´s disease (AD) is characterized by abundant amyloid plaques originating from the proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Compounds named γ-secretase modulators (GSMs)...

The intramembrane-cleaving protease γ-secretase catalyzes the last step in the generation of toxic amyloid-β (Aβ) peptides and is a principal therapeutic target in Alzheimer's disease. Both preclinical and clinical studies have demonstrated that inhibition of γ-secretase is associated with prohibitive side effects due to suppression of Notch proces...

The photo-probe AR366 inversely modulates γ-secretase and targets the N-terminal fragment of PSEN1. (A) Chemical structure of AR366, an inverse GSM photo-probe. AR366 was obtained through esterification of the carboxylic acid group in AR243. Note that, in contrast to AR243, the biotin moiety for affinity purification was placed on the alkynyl side...

Comprehensive evidence supports that oligomerization and accumulation of amyloidogenic Aβ42 peptides in brain is crucial in the pathogenesis of both familial and sporadic forms of Alzheimer's disease. Imaging studies indicate that the buildup of Aβ begins many years before the onset of clinical symptoms, and that subsequent neurodegeneration and co...