Biology subjects

Leptin, M.

Publications and source records attributed to Leptin, M..

4 recordsLinked to original sources

bioRxiv2018

Polarity sorting drives remodeling of actin-myosin networks

Cytoskeletal networks of actin filaments and myosin motors drive many dynamic cell processes. A key characteristic of these networks is their contractility. Despite intense experimental and theoretical efforts, it is not clear what mechanism favors network contraction over expansion. Recent work points to a dominant role for the nonlinear mechanical response of actin filaments, which can withstand stretching but buckle upon compression. Here we present an alternative mechanism. We study how interactions between actin and myosin-2 at the single filament level translate into contraction at the network scale by performing time-lapse imaging on reconstituted quasi-2D-networks mimicking the cell cortex. We observe myosin end-dwelling after it runs processively along actin filaments. This leads to transport and clustering of actin filament ends and the formation of transiently stable bipolar structures. Further we show that myosin-driven polarity sorting leads to polar actin aster formation, which act as contractile nodes that drive contraction in crosslinked networks. Computer simulations comparing the roles of the end-dwelling mechanism and a buckling-dependent mechanism show that the relative contribution of end-dwelling contraction increases as the network mesh-size decreases.

biophysics↗

bioRxiv2017

Dual Function For Tango1 In Secretion Of Bulky Cargo And In ER-Golgi Morphology

Tango1 helps the efficient delivery of large proteins to the cell surface. We show here that loss of Tango1, in addition to interfering with protein secretion, causes ER stress and defects in cell and ER/Golgi morphology. We find that the previously observed dependence of smaller cargos on Tango1 is a secondary effect, due to an indirect requirement: if large cargos like Dumpy, which we identify here as a new Tango1 cargo, are removed from the cell, non-bulky proteins re-enter the secretory pathway. Removal of the blocking cargo also attenuates the ER-stress response, and cell morphology is restored. Thus, failures in the secretion of non-bulky proteins, ER stress and defective cell morphology are secondary consequences of the retention of cargo. By contrast, the ERES defects in Tango1-depleted cells persist in the absence of bulky cargo, showing that they are due to a secretion-independent function of Tango1. Therefore, the maintenance of proper ERES architecture may be a primary function for Tango1.

cell biology↗

bioRxiv2017

A Theory That Predicts Behaviors Of Disordered Cytoskeletal Networks

Morphogenesis in animal tissues is largely driven by tensions of actomyosin networks, generated by an active contractile process that can be reconstituted in vitro. Although the network components and their properties are known, the requirements for contractility are still poorly understood. Here, we describe a theory that predicts whether an isotropic network will contract, expand, or conserve its dimensions. This analytical theory correctly predicts the behavior of simulated networks consisting of filaments with varying combinations of connectors, and reveals conditions under which networks of rigid filaments are either contractile or expansile. Our results suggest that pulsatility is an intrinsic behavior of contractile networks if the filaments are not stable but turn over. The theory offers a unifying framework to think about mechanisms of contractions or expansion. It provides a foundation for the study of a broad range of processes involving cytoskeletal networks, and a basis for designing synthetic networks.

cell biology↗

bioRxiv2017

Dynamics of ASC speck formation during skin inflammatory responses in vivo

Activated danger or pathogen sensors trigger assembly of the inflammasome adaptor ASC into specks, large signalling platforms considered hallmarks of inflammasome activation. Because a lack of in vivo tools has prevented the study of endogenous ASC dynamics, we generated a live ASC reporter through CRISPR/Cas9 tagging of the endogenous gene in zebrafish. We see strong ASC expression in the skin and other epithelia that act as barriers to insult. A toxic stimulus triggered speck formation and rapid pyroptosis in keratinocytes in vivo. Macrophages engulfed and digested this speck-containing pyroptotic debris. A 3D ultrastructural reconstruction based on CLEM of in vivo assembled specks revealed a compact network of highly intercrossed filaments, whereas PYD or CARD alone formed filamentous aggregates. The effector caspase is recruited through PYD, whose overexpression induced pyroptosis, but after substantial delay. Therefore, formation of a single compact speck and rapid cell death induction in vivo requires full-length ASC.\n\nOne Sentence SummaryWith a new endogenous ASC real-time reporter we characterize speck dynamics in vivo as well as the concomitant pyroptosis speck formation causes in keratinocytes.

immunology↗