Filter
Associated Lab
- Ahrens Lab (1) Apply Ahrens Lab filter
- Lippincott-Schwartz Lab (1) Apply Lippincott-Schwartz Lab filter
- Looger Lab (1) Apply Looger Lab filter
- Pachitariu Lab (1) Apply Pachitariu Lab filter
- Spruston Lab (1) Apply Spruston Lab filter
- Sternson Lab (1) Apply Sternson Lab filter
- Tebo Lab (1) Apply Tebo Lab filter
Publication Date
- January 28, 2022 (1) Apply January 28, 2022 filter
- January 24, 2022 (1) Apply January 24, 2022 filter
- January 19, 2022 (1) Apply January 19, 2022 filter
- January 18, 2022 (1) Apply January 18, 2022 filter
- January 15, 2022 (1) Apply January 15, 2022 filter
- January 12, 2022 (2) Apply January 12, 2022 filter
- January 10, 2022 (1) Apply January 10, 2022 filter
- January 7, 2022 (1) Apply January 7, 2022 filter
- January 5, 2022 (1) Apply January 5, 2022 filter
- January 4, 2022 (1) Apply January 4, 2022 filter
- January 1, 2022 (1) Apply January 1, 2022 filter
- Remove January 2022 filter January 2022
- Remove 2022 filter 2022
12 Janelia Publications
Showing 11-12 of 12 resultsNicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method to examine the cellular and subcellular pharmacokinetic properties of these compounds in living cells. Here, we developed new intensity-based drug sensing fluorescent reporters ('iDrugSnFRs') for the nicotinic partial agonists dianicline, cytisine, and two cytisine derivatives - 10-fluorocytisine and 9-bromo-10-ethylcytisine. We report the first atomic-scale structures of liganded periplasmic binding protein-based biosensors, accelerating development of iDrugSnFRs and also explaining the activation mechanism. The nicotinic iDrugSnFRs detect their drug partners in solution, as well as at the plasma membrane (PM) and in the endoplasmic reticulum (ER) of cell lines and mouse hippocampal neurons. At the PM, the speed of solution changes limits the growth and decay rates of the fluorescence response in almost all cases. In contrast, we found that rates of membrane crossing differ among these nicotinic drugs by > 30 fold. The new nicotinic iDrugSnFRs provide insight into the real-time pharmacokinetic properties of nicotinic agonists and provide a methodology whereby iDrugSnFRs can inform both pharmaceutical neuroscience and addiction neuroscience.
Organelles move along differentially modified microtubules to establish and maintain their proper distributions and functions. However, how cells interpret these post-translational microtubule modification codes to selectively regulate organelle positioning remains largely unknown. The endoplasmic reticulum (ER) is an interconnected network of diverse morphologies that extends promiscuously throughout the cytoplasm, forming abundant contacts with other organelles. Dysregulation of endoplasmic reticulum morphology is tightly linked to neurologic disorders and cancer. Here we demonstrate that three membrane-bound endoplasmic reticulum proteins preferentially interact with different microtubule populations, with CLIMP63 binding centrosome microtubules, kinectin (KTN1) binding perinuclear polyglutamylated microtubules, and p180 binding glutamylated microtubules. Knockout of these proteins or manipulation of microtubule populations and glutamylation status results in marked changes in endoplasmic reticulum positioning, leading to similar redistributions of other organelles. During nutrient starvation, cells modulate CLIMP63 protein levels and p180-microtubule binding to bidirectionally move endoplasmic reticulum and lysosomes for proper autophagic responses.