Structure and membrane compartments

Team Publications

Year of publication 2018

Léa Ripoll, Xavier Heiligenstein, Ilse Hurbain, Lia Domingues, Florent Figon, Karl J Petersen, Megan K Dennis, Anne Houdusse, Michael S Marks, Graça Raposo, Cédric Delevoye (2018 Jun 8)

Myosin VI and branched actin filaments mediate membrane constriction and fission of melanosomal tubule carriers.

The Journal of cell biology : 2709-2726 : DOI : 10.1083/jcb.201709055 Learn more

Vesicular and tubular transport intermediates regulate organellar cargo dynamics. Transport carrier release involves local and profound membrane remodeling before fission. Pinching the neck of a budding tubule or vesicle requires mechanical forces, likely exerted by the action of molecular motors on the cytoskeleton. Here, we show that myosin VI, together with branched actin filaments, constricts the membrane of tubular carriers that are then released from melanosomes, the pigment containing lysosome-related organelles of melanocytes. By combining superresolution fluorescence microscopy, correlative light and electron microscopy, and biochemical analyses, we find that myosin VI motor activity mediates severing by constricting the neck of the tubule at specific melanosomal subdomains. Pinching of the tubules involves the cooperation of the myosin adaptor optineurin and the activity of actin nucleation machineries, including the WASH and Arp2/3 complexes. The fission and release of these tubules allows for the export of components from melanosomes, such as the SNARE VAMP7, and promotes melanosome maturation and transfer to keratinocytes. Our data reveal a new myosin VI- and actin-dependent membrane fission mechanism required for organelle function.

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Philip D Stahl, Graça Raposo (2018 May 17)

Exosomes and extracellular vesicles: the path forward.

Essays in biochemistry : 119-124 : DOI : 10.1042/EBC20170088 Learn more

Over the course of the past several decades, the concept that extracellular vesicles, exosomes and microvesicles, operate as cellular “housekeepers” and as agents for communication between and among cells and tissues, has emerged into one of the most promising yet vexing problems facing the biomedical community. Already, extracellular vesicles from biological fluids are being used for diagnostic purposes and hopes abound for their use as therapeutic agents. However, the most basic mechanistic questions surrounding their biogenesis and function in cellular and tissue homeostasis remain largely unexplored. In this issue of , the rise of a new intercellular communications pathway is considered from many perspectives-cell biology, physiology, and pathophysiology.

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Cécile Campagne, Léa Ripoll, Floriane Gilles-Marsens, Graça Raposo, Cédric Delevoye (2018 Feb 15)

AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis.

International journal of molecular sciences : DOI : E568 Learn more

Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D-reconstructed pigmented epidermis decreases pigmentation by impacting the maturation of melanosomes in fully pigmented organelles. This study highlights that peptides targeting the intracellular trafficking of melanocytes are candidate molecules to tune pigmentation in health and disease.

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Guillaume van Niel, Gisela D'Angelo, Graça Raposo (2018 Jan 18)

Shedding light on the cell biology of extracellular vesicles.

Nature reviews. Molecular cell biology : 213-228 : DOI : 10.1038/nrm.2017.125 Learn more

Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.

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