An ion channel on steroids: the unconventional pathway of calcium regulation by endogenous cannabinoidsPolina Lishko, PhD Assistant Professor of Cell and Developmental Biology Department of Molecular and Cell Biology UC Berkeley Host: Sharona Gordon Ion channels control sperm activity by regulating intracellular levels of calcium, which stimulates cell motility and fertility. Steroid hormone progesterone produced by an ovulated egg promotes the entry of calcium through sperm channel CatSper- an event so central for fertilization that men lacking these channels are infertile. We have demonstrated that human CatSper is associated with a membrane progesterone receptor, which makes human spermatozoa controlled by the female reproductive cycle. The identity of this receptor has been recently revealed to be serine hydrolase ABHD2 that degrades endogenous CatSper inhibitor 2-arachidonoylglycerol upon progesterone exposure. ABHD2 is ubiquitously expressed, and the pathway we have discovered in spermatozoa, is likely a universal pathway that defines membrane steroid signaling in other tissues.
Collective endothelial cell migration – cadherin fingers lead the wayArnold L. Hayer, Ph.D. Department of Chemical and Systems Biology Stanford University Abstract: The development and maintenance of the vasculature requires collective cell movement, during which neighboring cells coordinate the polarity of their migration machineries. We addressed the unresolved question of how polarity signals are transmitted from one cell to another across symmetrical cadherin junctions, using an in vitro model of collective endothelial cell migration. We found that collectively migrating endothelial cells have polarized VE-cadherin-rich membrane protrusions, ‘cadherin fingers’, which leading cells extend from their rear and follower cells engulf at their front. In follower cells, engulfment of cadherin fingers occurs along with the formation of a lamellipodia-like zone with low actomyosin contractility, and requires VE-cadherin/catenin complexes and Arp2/3-driven actin polymerization. Lateral accumulation of cadherin fingers in follower cells precedes turning, and increased actomyosin contractility can initiate cadherin finger extension as well as engulfment by a neighboring cell, to promote follower behavior. Cadherin fingers create positively curved membrane surfaces only in the front of follower cells, which selectively recruit and polarize curvature sensing regulatory proteins. Thus, engulfment of cadherin fingers at the cell front converts symmetric cadherin junctions into polarized structures that support collective cell guidance. Further, I will discuss our recent identification of a BAR domain and RhoGAP protein, which is required both for coordinated endothelial cell movement and vascular sprouting in vitro, and therefore establishes an intriguing mechanistic link between the asymmetric cadherin finger structure and RhoGTPase signaling. host: Stan Froehner
Couple, amplify, fire!
Coupling of L-type calcium channels and excitabilityL-type CaV1.2 and CaV1.3 calcium channels are key players in the generation and regulation of electrical activity in different cell types, including neurons and myocytes. In the pacemaker cells of the heart, the spike of the action potential that initiates each heartbeat depends entirely on the entry of calcium through these channels. Recently, we discovered a novel cooperative gating mechanism, on both CaV1.2 and CaV1.3 channels, which facilitates calcium entry and modulates the excitability of ventricular cardiomyocytes and neurons. We found that these channels establish a calcium-dependent physical interaction via their c-termini, which results in an increase in their open probability. Our more recent project aims to answer two new questions: Do CaV1.2 and CaV1.3 channel undergo functional coupling in the pacemaking cells of the heart? And, if so, is this coupling modulated by physiological stimuli? Our new results point to a mechanism by which beta-adrenergic signaling increases the coupling of CaV1.2 channels in the pacemaker cells. These exciting results add to our understanding on how the sympathetic nervous system increases heart rate. Claudia Moreno, Ph.D. Department of Physiology and Membrane Biology School of Medicine University of California, Davis host: Stan Froehner
How plants conquer the space: the cell’s flying plates
Plant cytokinesis is orchestrated by a specialized structure, the phragmoplast. The phragmoplast first occurred in representatives of Charophyte algae and then became the main division apparatus in land plants. Major cellular activities, including cytoskeletal dynamics, vesicle trafficking, membrane assembly, and cell wall biosynthesis, cooperate in the phragmoplast under the guidance of a complex signaling network. My research focuses on the self-organization processes that govern phragmoplast functions. I will give a general overview of plant cytokinesis, and present our recent data on the gamma-tubulin independent microtubule nucleation by the plant-specific protein MACERATOR and a conserved member of TPX2 protein family.Andrei Smertenko, Ph.D. Assistant Professor, Molecular Plant Sciences Washington State University host: Linda Wordeman
High spatiotemporal resolution, three-dimension fluorescence imaging of biological samples in vivoDr. Liangyi Chen Professor Laboratory of Cell Secretion and Metabolism Institute of Molecular Medicine, Peking University, Beijing, China Host: Bertil Hille Abstract: I will give two stories. (i) One story describes unpublished ultrasensitive Hessian structured illumination microscopy that enables ultrafast and long-term super-resolution (SR) live-cell imaging. At a photon dose one order less than point-scanning microscopy, Hessian-SIM has achieved 88-nm and 188-Hz spatial-temporal resolution for live cells imaging and lasted thousands of images without artifacts. Operating at 1 Hz, Hessian-SIM enables hour-long, time-lapse SR imaging with mitigatable photobleaching, highlighting the possibility of achieving SR imaging with commonly used fluorophores for an unlimited period of time. (ii) The second story is our recent Nature Methods paper, our invention of the fast high-resolution miniature two-photon microscope for brain imaging in freely-behaving mice at the single-spine level. With a headpiece weighing 2.15 g and a new type of hollow-core photonic crystal fiber to deliver 920-nm femtosecond laser pulses, the mini-microscope is capable of imaging commonly used biosensors at high spatiotemporal resolution (0.64 μm laterally and 3.35 μm axially, 40 Hz at 256 × 256 pixels). It compares favorably with benchtop two-photon microscopy and miniature wide-field fluorescence microscopy in the structural and functional imaging of Thy1-GFP- or GCaMP6f-labeled neurons. Further, we demonstrate its unique application and robustness with hour-long recording of neuronal activities down to the level of spines in mice experiencing vigorous body and head movements or engaging in social interaction.
Evolution and brain computationI will introduce our work towards identifying principles of brain function and computation, focused on using comparative approaches and exploiting unusual model systems (reptiles, cephalopods) to study sleep, texture perception and cerebral cortex evolution. Gilles Laurent, PhD, DVM Director Max Planck Institute for Brain Research http://www.brain.mpg.de/home/ 4:00 PM Location: T-739, HSB host: Stan Froehner
Dr. Bastian’s seminar will be rescheduled for a later date.