Illuminating the dark side of recycling endosomes

Ripoll, Léa; Heiligenstein, Xavier; Raposo, Graça; Delevoye, Cédric

doi:10.1080/15384101.2016.1160682

Cited by 7 publications

(5 citation statements)

References 7 publications

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“…52 While pharmacological, genetic, and immunohistochemical evidence 47,50,53 suggests that inhibition of NMIIB, rather than NMIIA or NMIIC, likely underlies the effects of blebbistatin and BHC analogues on neurotransmission observed in this study, we cannot rule out effects on other nonmuscle myosins such as myosin VI, which also regulates synaptic transmission and is sensitive to blebbistatin. 54 The models of the BHC analogues bound to myosin at the blebbistatin site provide insights that are generally consistent with the SAR trends summarized above. Importantly, the side arms of the BHC analogues appear to interact with the hydrophobic residues lining an extension of the binding pocket, which accommodates the longest side arm length of 6i (six carbons) and might accommodate the longer side chains in new analogues.…”

Section: Discussionsupporting

confidence: 67%

Synthesis and Evaluation of 4-Hydroxycoumarin Imines as Inhibitors of Class II Myosins

et al. 2020

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B. C.C. and R.K.B. conducted the motility assays and analyzed the data. D.H. and T.G. did the muscle experiments and analyzed the data. A.I. performed the solubility and stability measurements, recorded all UV/visible spectra in methanol, and determined the λ max and ε values. ASSOCIATED CONTENT Supporting InformationThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c01062. UV-visible spectra for hydrolysis of 7i in 99:1 (v/v) PBS/methanol; PDB files for the homology models of bovine cardiac and rabbit skeletal myosins (used for Table 2 and Figure 7) (PDF) SMILES strings for all of the new compounds tested (CSV)

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Section: Discussionsupporting

confidence: 67%

Synthesis and Evaluation of 4-Hydroxycoumarin Imines as Inhibitors of Class II Myosins

et al. 2020

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“…The WASH complex promotes the Arp2/3-dependent actin polymerization on early endosomes to facilitate the release of recycling tubular intermediates in most cell types (Derivery et al, 2009; Gomez and Billadeau, 2009). In melanocytes, the WASH complex can be recruited to early endosomes (Tyrrell et al, 2016) but does not participate in the anterograde delivery of cargoes from endosomes to melanosomes (Delevoye et al, 2016; Ripoll et al, 2016). Consistently, gene targeting of the WASH complex subunit strumpellin in mice does not lead to hypopigmentation (Tyrrell et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

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

Ripoll

Heiligenstein

Hurbain

et al. 2018

Journal of Cell Biology

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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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“…The eight-subunit biogenesis of lysosome-related organelles complex 1 (BLOC-1) is required for the elongation and release of nascent RE tubular carriers from SE in coordination with the microtubule-based kinesin-3 motor KIF13A and actin-related machineries ( Ripoll et al, 2016 ; Delevoye et al, 2014 , 2016 ; Shakya et al, 2018 ; Thankachan and Setty, 2022 ). Certain BLOC-1-dependent RE carriers deliver a subset of cargoes to LROs in specialized cell types, such as melanosomes in pigment cells, and loss of BLOC-1 function underlies several subtypes of HPS ( Bowman et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

PI4P and BLOC-1 remodel endosomal membranes into tubules

Jani

Cicco

Keren-Kaplan

et al. 2022

Journal of Cell Biology

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Intracellular trafficking is mediated by transport carriers that originate by membrane remodeling from donor organelles. Tubular carriers contribute to the flux of membrane lipids and proteins to acceptor organelles, but how lipids and proteins impose a tubular geometry on the carriers is incompletely understood. Using imaging approaches on cells and in vitro membrane systems, we show that phosphatidylinositol-4-phosphate (PI4P) and biogenesis of lysosome-related organelles complex 1 (BLOC-1) govern the formation, stability, and functions of recycling endosomal tubules. In vitro, BLOC-1 binds and tubulates negatively charged membranes, including those containing PI4P. In cells, endosomal PI4P production by type II PI4-kinases is needed to form and stabilize BLOC-1-dependent recycling endosomal tubules. Decreased PI4KIIs expression impairs the recycling of endosomal cargoes and the life cycles of intracellular pathogens such as Chlamydia bacteria and influenza virus that exploit the membrane dynamics of recycling endosomes. This study demonstrates how a phospholipid and a protein complex coordinate the remodeling of cellular membranes into functional tubules.

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Illuminating the dark side of recycling endosomes

Cited by 7 publications

References 7 publications

Synthesis and Evaluation of 4-Hydroxycoumarin Imines as Inhibitors of Class II Myosins

Synthesis and Evaluation of 4-Hydroxycoumarin Imines as Inhibitors of Class II Myosins

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

PI4P and BLOC-1 remodel endosomal membranes into tubules

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