Kinetic and photonic techniques to study chemotactic signaling in sea urchin sperm.

Sperm from sea urchins are attracted by chemical cues released by the egg-a mechanism called chemotaxis. We describe here the signaling pathway and molecular components endowing sperm with single-molecule sensitivity. Chemotactic signaling and behavioral responses occur on a timescale of a few milliseconds to seconds.

Orthogonally Photocontrolled Non-Autonomous DNA Walker.

There is considerable interest in developing progressively moving devices on the nanoscale, with the aim of using them as parts of programmable therapeutics, smart materials, and nanofactories. Present here is an entirely light-induced DNA walker based on orthogonal photocontrol. Implementing two azobenzene derivatives, S-DM-Azo and DM-Azo, enabled precise coordination of strand displacement reactions that powered a biped walker and guided it along a defined track in a non-autonomous way.

Species-specific differences in nonlysosomal glucosylceramidase GBA2 function underlie locomotor dysfunction arising from loss-of-function mutations.

The nonlysosomal glucosylceramidase β2 (GBA2) catalyzes the hydrolysis of glucosylceramide to glucose and ceramide. Mutations in the human gene have been associated with hereditary spastic paraplegia (HSP), autosomal-recessive cerebellar ataxia (ARCA), and the Marinesco-Sjögren-like syndrome. However, the underlying molecular mechanisms are ill-defined.

Nonlinear Processing of Shape Information in Rat Lateral Extrastriate Cortex.

In rodents, the progression of extrastriate areas located laterally to primary visual cortex (V1) has been assigned to a putative object-processing pathway (homologous to the primate ventral stream), based on anatomical considerations. Recently, we found functional support for such attribution (Tafazoli et al., 2017), by showing that this cortical progression is specialized for coding object identity despite view changes, the hallmark property of a ventral-like pathway.

⁻A Simple Analysis Software to Comprehensively Study Flagellar Beating and Sperm Steering.

Motile cilia, also called flagella, are found across a broad range of species; some cilia propel prokaryotes and eukaryotic cells like sperm, while cilia on epithelial surfaces create complex fluid patterns e.g., in the brain or lung.

Potassium channel-based optogenetic silencing.

Optogenetics enables manipulation of biological processes with light at high spatio-temporal resolution to control the behavior of cells, networks, or even whole animals. In contrast to the performance of excitatory rhodopsins, the effectiveness of inhibitory optogenetic tools is still insufficient. Here we report a two-component optical silencer system comprising photoactivated adenylyl cyclases (PACs) and the small cyclic nucleotide-gated potassium channel SthK.

Precipitation with polyethylene glycol followed by washing and pelleting by ultracentrifugation enriches extracellular vesicles from tissue culture supernatants in small and large scales.

Extracellular vesicles (EVs) provide a complex means of intercellular signalling between cells at local and distant sites, both within and between different organs. According to their cell-type specific signatures, EVs can function as a novel class of biomarkers for a variety of diseases, and can be used as drug-delivery vehicles. Furthermore, EVs from certain cell types exert beneficial effects in regenerative medicine and for immune modulation.

CCL17 exerts a neuroimmune modulatory function and is expressed in hippocampal neurons.

Chemokines are important signaling molecules in the immune and nervous system. Using a fluorescence reporter mouse model, we demonstrate that the chemokine CCL17, a ligand of the chemokine receptor CCR4, is produced in the murine brain, particularly in a subset of hippocampal CA1 neurons. We found that basal expression of Ccl17 in hippocampal neurons was strongly enhanced by peripheral challenge with lipopolysaccharide (LPS).

Neuronal correlates of motion-defined shape perception in primate dorsal and ventral streams.

Human and non-human primates can readily perceive the shape of objects using visual motion. Classically, shape, and motion are considered to be separately processed via ventral and dorsal cortical pathways, respectively. However, many lines of anatomical and physiological evidence have indicated that these two pathways are likely to be interconnected at some stage.

The solute carrier SLC9C1 is a Na/H-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding.

Voltage-sensing (VSD) and cyclic nucleotide-binding domains (CNBD) gate ion channels for rapid electrical signaling. By contrast, solute carriers (SLCs) that passively redistribute substrates are gated by their substrates themselves. Here, we study the orphan sperm-specific solute carriers SLC9C1 that feature a unique tripartite structure: an exchanger domain, a VSD, and a CNBD.

New role of P2X7 receptor in an Alzheimer's disease mouse model.

Extracellular aggregates of amyloid β (Aβ) peptides, which are characteristic of Alzheimer's disease (AD), act as an essential trigger for glial cell activation and the release of ATP, leading to the stimulation of purinergic receptors, especially the P2X7 receptor (P2X7R). However, the involvement of P2X7R in the development of AD is still ill-defined regarding the dual properties of this receptor. Particularly, P2X7R activates the NLRP3 inflammasome leading to the release of the pro-inflammatory cytokine, IL-1β; however, P2X7R also induces cleavage of the amyloid precursor protein generating Aβ peptides or the neuroprotective fragment sAPPα.

Cannabinoid Receptor 2-Deficiency Ameliorates Disease Symptoms in a Mouse Model with Alzheimer's Disease-Like Pathology.

It is widely accepted that the endocannabinoid system (ECS) is a modulator of neuroinflammation associated with neurodegenerative disorders, including Alzheimer's disease (AD). Thus, expression of the cannabinoid receptor 2 (CB2) is induced in plaque-associated microglia and astrocytes in brain tissues from AD patients and in genetic mouse models expressing pathogenic variants of the amyloid precursor protein (APP). However, the exact mechanism of CB2 signaling in this mouse model remains elusive, because the genetic deletion of CB2 and the pharmacological activation of CB2 both reduced neuroinflammation.

A novel cross-species inhibitor to study the function of CatSper Ca channels in sperm.

Background And Purpose: Sperm from many species share the sperm-specific Ca channel CatSper that controls the intracellular Ca concentration and, thereby, the swimming behaviour. A growing body of evidence suggests that the mechanisms controlling the activity of CatSper and its role during fertilization differ among species. A lack of suitable pharmacological tools has hampered the elucidation of the function of CatSper.

A bio-hybrid DNA rotor-stator nanoengine that moves along predefined tracks.

Biological motors are highly complex protein assemblies that generate linear or rotary motion, powered by chemical energy. Synthetic motors based on DNA nanostructures, bio-hybrid designs or synthetic organic chemistry have been assembled. However, unidirectionally rotating biomimetic wheel motors with rotor-stator units that consume chemical energy are elusive.

Poly-ligand profiling differentiates trastuzumab-treated breast cancer patients according to their outcomes.

Assessing the phenotypic diversity underlying tumour progression requires the identification of variations in the respective molecular interaction networks. Here we report proof-of-concept for a platform called poly-ligand profiling (PLP) that surveys these system states and distinguishes breast cancer patients who did or did not derive benefit from trastuzumab. We perform tissue-SELEX on breast cancer specimens to enrich single-stranded DNA (ssDNA) libraries that preferentially interact with molecular components associated with the two clinical phenotypes.

Inhibitor-Directed Spin Labelling-A High Precision and Minimally Invasive Technique to Study the Conformation of Proteins in Solution.

Pulsed electron-electron double resonance spectroscopy (known as PELDOR or DEER) has recently become a very popular tool in structural biology. The technique can be used to accurately measure distance distributions within macromolecules or macromolecular complexes, and has become a standard method to validate structural models and to study the conformational flexibility of macromolecules. It can be applied in solution, in lipid environments or even in cells.

Mechanistic insights into the role of prenyl-binding protein PrBP/δ in membrane dissociation of phosphodiesterase 6.

Isoprenylated proteins are associated with membranes and their inter-compartmental distribution is regulated by solubilization factors, which incorporate lipid moieties in hydrophobic cavities and thereby facilitate free diffusion during trafficking. Here we report the crystal structure of a solubilization factor, the prenyl-binding protein (PrBP/δ), at 1.81 Å resolution in its ligand-free apo-form.

The SWI/SNF subunit Bcl7a contributes to motor coordination and Purkinje cell function.

Chromatin remodelers have emerged as prominent regulators of epigenetic processes and potential drivers of various human pathologies. The multi-subunit chromatin-remodeling SWI/SNF complex determines gene expression programs and, consequently, contributes to the differentiation, maturation and plasticity of neurons. Here, we investigate the elusive biological function of Bcl7a and Bcl7b, two newly identified subunits of the SWI/SNF complex that are highly expressed throughout the brain.

Shedding light on the role of cAMP in mammalian sperm physiology.

Mammalian fertilization relies on sperm finding the egg and penetrating the egg vestments. All steps in a sperm's lifetime crucially rely on changes in the second messenger cAMP (cyclic adenosine monophosphate). In recent years, it has become clear that signal transduction in sperm is not a continuum, but rather organized in subcellular domains, e.

Human sperm steer with second harmonics of the flagellar beat.

Sperm are propelled by bending waves traveling along their flagellum. For steering in gradients of sensory cues, sperm adjust the flagellar waveform. Symmetric and asymmetric waveforms result in straight and curved swimming paths, respectively.

"Silent" NMDA Synapses Enhance Motion Sensitivity in a Mature Retinal Circuit.

Retinal direction-selective ganglion cells (DSGCs) have the remarkable ability to encode motion over a wide range of contrasts, relying on well-coordinated excitation and inhibition (E/I). E/I is orchestrated by a diverse set of glutamatergic bipolar cells that drive DSGCs directly, as well as indirectly through feedforward GABAergic/cholinergic signals mediated by starburst amacrine cells. Determining how direction-selective responses are generated across varied stimulus conditions requires understanding how glutamate, acetylcholine, and GABA signals are precisely coordinated.

Photocontrol of the Hv1 Proton Channel.

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.

Intracellular activation of ovastacin mediates pre-fertilization hardening of the zona pellucida.

Study Question: How and where is pro-ovastacin activated and how does active ovastacin regulate zona pellucida hardening (ZPH) and successful fertilization?

Study Finding: Ovastacin is partially active before exocytosis and pre-hardens the zona pellucida (ZP) before fertilization.

What Is Known Already: The metalloproteinase ovastacin is stored in cortical granules, it cleaves zona pellucida protein 2 (ZP2) upon fertilization and thereby destroys the ZP sperm ligand and triggers ZPH. Female mice deficient in the extracellular circulating ovastacin-inhibitor fetuin-B are infertile due to pre-mature ZPH.

Endocytic sorting motif interactions involved in Nef-mediated downmodulation of CD4 and CD3.

Lentiviral Nefs recruit assembly polypeptide complexes and target sorting motifs in cellular receptors to induce their internalization. While Nef-mediated CD4 downmodulation is conserved, the ability to internalize CD3 was lost in HIV-1 and its precursors. Although both functions play key roles in lentiviral replication and pathogenicity, the underlying structural requirements are poorly defined.