A5071387121- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Photoreceptor and optogenetics research
- Retinal Development and Disorders
- Neuroscience and Neuropharmacology Research
- Toxin Mechanisms and Immunotoxins
- Neural dynamics and brain function
University of Münster
2023
The University of Sydney
2013-2015
Children's Medical Research Institute
2013-2015
Dynamin GTPase activity increases when it oligomerizes either into helices in the presence of lipid templates or rings SH3 domain proteins. Dynasore is a dynamin inhibitor moderate potency ( IC 50 ˜ 15 μM vitro ). We show that dynasore binds stoichiometrically to detergents used for drug screening, drastically reducing its = 479 μM) and research tool utility. synthesized focused set dihydroxyl trihydroxyl analogs called Dyngo™ compounds, five which had improved potency, reduced detergent...
Chlorpromazine is a phenothiazine‐derived antipsychotic drug ( APD ) that inhibits clathrin‐mediated endocytosis CME in cells by an unknown mechanism. We examined whether its action and of other APDs might be mediated the GTPase activity dynamin. Eight eight inhibited dynamin I dynI 2–12 µ m range, most potent being trifluoperazine IC 50 2.6 ± 0.7 ). They also II dynII at similar concentrations. Typical atypical not based on phenothiazine scaffold were 8‐ to 10‐fold less (haloperidol...
Compensatory endocytosis is crucial for the presynapse to maintain a functional pool of fusion-competent vesicles. Slow Clathrin-mediated has been widely regarded as primary mechanism retrieval but this challenged by competing Clathrin-independent endocytic models, most notably sub-second ultra-fast endocytosis, reported be predominant at physiological temperature. Here, we sought resolve salience respective modes using purely presynaptic preparation, Xenapse, amenable total internal...
Neurons use Clathrin-mediated endocytosis to retrieve synaptic vesicle (SV) proteins during compensatory after presynaptic SV fusion. We have shown cargo be re-sorted and pre-assembled outside the active zone into Clathrin-coated structures (CCS) of variable size curvature, constituting a readily retrievable pool. During CCS pool must remodeled swiftly spherical vesicles within 10 seconds at physiological temperature. How this is achieved remains elusive. Here we performed live-cell imaging...
The primary unit of exocytosis, the synaptic vesicle, is replete with proteins which enable vesicle fusion. For maintaining transmission have to be rapidly cleared from active zone. immediate fate cargo post-fusion and precise mechanism its resorting into a readily retrievable pool (RRetP) for endocytosis remains unclear. To address this, we developed purely presynaptic preparation, xenapse, boutons formed en face directly onto glass coverslip enabling optical single recording by total...
Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3) domains. At least 30 SH3 domain-containing bind dynamin at proline-rich domain (PRD). Those that stimulate activity act by promoting oligomerisation. We undertook systematic parallel screening of 13 glutathione-S-transferase (GST)-tagged endocytosis-related domains...