eLife
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Co-agonists differentially tune GluN2B-NMDA receptor trafficking at hippocampal synapsesThe subunit composition of synaptic NMDA receptors (NMDAR), such as the relative content of GluN2A- and GluN2B-containing receptors, greatly influences the glutamate synaptic transmission. Receptor co-agonists, glycine and D-serine, have intriguingly emerged as potential regulators of the receptor trafficking in addition to their requirement for its activation. Using a combination of singl... ...
eLife - Tập 6
Direction-dependent arm kinematics reveal optimal integration of gravity cuesThe brain has evolved an internal model of gravity to cope with life in the Earth's gravitational environment. How this internal model benefits the implementation of skilled movement has remained unsolved. One prevailing theory has assumed that this internal model is used to compensate for gravity's mechanical effects on the body, such as to maintain invariant motor trajectories. Alternati... ...
eLife - Tập 5
Structural insights into the light-driven auto-assembly process of the water-oxidizing Mn4CaO5-cluster in photosystem IIIn plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn4CaO5-cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural informatio... ...
eLife - Tập 6
Structural mechanisms of phospholipid activation of the human TPC2 channelMammalian two-pore channels (TPCs) regulate the physiological functions of the endolysosome. Here we present cryo-EM structures of human TPC2 (HsTPC2), a phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2)-activated, Na+ selective channel, in the ligand-bound and apo states. The apo structure captures the closed conformation, while the ligand-bound form features the channel in both open and ... ...
eLife - Tập 8
Regulation of mTORC1 by lysosomal calcium and calmodulinBlockade of lysosomal calcium release due to lysosomal lipid accumulation has been shown to inhibit mTORC1 signaling. However, the mechanism by which lysosomal calcium regulates mTORC1 has remained undefined. Herein we report that proper lysosomal calcium release through the calcium channel TRPML1 is required for mTORC1 activation. TRPML1 depletion inhibits mTORC1 activity, while overexpre... ...
eLife - Tập 5
Agonist-specific voltage-dependent gating of lysosomal two-pore Na+ channelsMammalian two-pore-channels (TPC1, 2; TPCN1, TPCN2) are ubiquitously- expressed, PI(3,5)P2-activated, Na+-selective channels in the endosomes and lysosomes that regulate luminal pH homeostasis, membrane trafficking, and Ebola viral infection. Whereas the channel activity of TPC1 is strongly dependent on membrane voltage, TPC2 lacks such voltage dependence despite the presence of the presum... ...
eLife - Tập 8
Selective agonist of TRPML2 reveals direct role in chemokine release from innate immune cellsCytokines and chemokines are produced and secreted by a broad range of immune cells including macrophages. Remarkably, little is known about how these inflammatory mediators are released from the various immune cells. Here, the endolysosomal cation channel TRPML2 is shown to play a direct role in chemokine trafficking and secretion from murine macrophages. To demonstrate acute and direct i... ...
eLife - Tập 7
Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal functionIon selectivity is a defining feature of a given ion channel and is considered immutable. Here we show that ion selectivity of the lysosomal ion channel TPC2, which is hotly debated (Calcraft et al., 2009; Guo et al., 2017; Jha et al., 2014; Ruas et al., 2015; Wang et al., 2012), depends on the activating ligand. A high-throughput screen identified two structurally distinct TPC2 agonists. ... ...
eLife - Tập 9
Engineering induction of singular neural rosette emergence within hPSC-derived tissuesHuman pluripotent stem cell (hPSC)-derived neural organoids display unprecedented emergent properties. Yet in contrast to the singular neuroepithelial tube from which the entire central nervous system (CNS) develops in vivo, current organoid protocols yield tissues with multiple neuroepithelial units, a.k.a. neural rosettes, each acting as independent morphogenesis centers and thereby conf... ...
eLife - Tập 7
Analysis of cellular behavior and cytoskeletal dynamics reveal a constriction mechanism driving optic cup morphogenesisContractile actomyosin networks have been shown to power tissue morphogenesis. Although the basic cellular machinery generating mechanical tension appears largely conserved, tensions propagate in unique ways within each tissue. Here we use the vertebrate eye as a paradigm to investigate how tensions are generated and transmitted during the folding of a neuroepithelial layer. We record memb... ...
eLife - Tập 5
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