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  1. Article ; Online: Reply to: "Overlapping Ranges in Levels Indicate That Hexosylsphingosine Is Not a Clinically Relevant Biomarker for GBA1-Associated Parkinson's Disease".

    Gleason, Adenrele M / Tayebi, Nahid / Lopez, Grisel J / Sidransky, Ellen

    Movement disorders : official journal of the Movement Disorder Society

    2022  Volume 37, Issue 8, Page(s) 1781–1782

    MeSH term(s) Biomarkers ; Glucosylceramidase/genetics ; Humans ; Mutation ; Parkinson Disease/diagnosis ; Parkinson Disease/genetics ; alpha-Synuclein
    Chemical Substances Biomarkers ; alpha-Synuclein ; Glucosylceramidase (EC 3.2.1.45)
    Language English
    Publishing date 2022-09-15
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Intramural ; Comment
    ZDB-ID 607633-6
    ISSN 1531-8257 ; 0885-3185
    ISSN (online) 1531-8257
    ISSN 0885-3185
    DOI 10.1002/mds.29131
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2555: Show issues Location:
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    Zs.MO 238: Show issues

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  2. Article ; Online: Syndapin and GTPase RAP-1 control endocytic recycling via RHO-1 and non-muscle myosin II.

    Rodriguez-Polanco, Wilmer R / Norris, Anne / Velasco, Agustin B / Gleason, Adenrele M / Grant, Barth D

    Current biology : CB

    2023  Volume 33, Issue 22, Page(s) 4844–4856.e5

    Abstract: After endocytosis, many plasma membrane components are recycled via membrane tubules that emerge from early endosomes to form recycling endosomes, eventually leading to their return to the plasma membrane. We previously showed that Syndapin/PACSIN-family ...

    Abstract After endocytosis, many plasma membrane components are recycled via membrane tubules that emerge from early endosomes to form recycling endosomes, eventually leading to their return to the plasma membrane. We previously showed that Syndapin/PACSIN-family protein SDPN-1 is required in vivo for basolateral endocytic recycling in the C. elegans intestine. Here, we document an interaction between the SDPN-1 SH3 domain and a target sequence in PXF-1/PDZ-GEF1/RAPGEF2, a known exchange factor for Rap-GTPases. We found that endogenous mutations engineered into the SDPN-1 SH3 domain, or its binding site in the PXF-1 protein, interfere with recycling in vivo, as does the loss of the PXF-1 target RAP-1. In some contexts, Rap-GTPases negatively regulate RhoA activity, suggesting a potential for Syndapin to regulate RhoA. Our results indicate that in the C. elegans intestine, RHO-1/RhoA is enriched on SDPN-1- and RAP-1-positive endosomes, and the loss of SDPN-1 or RAP-1 elevates RHO-1(GTP) levels on intestinal endosomes. Furthermore, we found that depletion of RHO-1 suppressed sdpn-1 mutant recycling defects, indicating that control of RHO-1 activity is a key mechanism by which SDPN-1 acts to promote endocytic recycling. RHO-1/RhoA is well known for controlling actomyosin contraction cycles, although little is known about the effects of non-muscle myosin II on endosomes. Our analysis found that non-muscle myosin II is enriched on SDPN-1-positive endosomes, with two non-muscle myosin II heavy-chain isoforms acting in apparent opposition. Depletion of nmy-2 inhibited recycling like sdpn-1 mutants, whereas depletion of nmy-1 suppressed sdpn-1 mutant recycling defects, indicating that actomyosin contractility controls recycling endosome function.
    MeSH term(s) Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans/metabolism ; GTP Phosphohydrolases/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Actomyosin/metabolism ; Endocytosis/physiology ; Endosomes/metabolism ; Myosin Type II/metabolism
    Chemical Substances GTP Phosphohydrolases (EC 3.6.1.-) ; Caenorhabditis elegans Proteins ; Actomyosin (9013-26-7) ; Myosin Type II (EC 3.6.1.-)
    Language English
    Publishing date 2023-10-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2023.09.051
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3208: Show issues Location:
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  3. Article: Syndapin Regulates the RAP-1 GTPase to Control Endocytic Recycling via RHO-1 and Non-Muscle Myosin II.

    Rodriguez-Polanco, Wilmer R / Norris, Anne / Velasco, Agustin B / Gleason, Adenrele M / Grant, Barth D

    bioRxiv : the preprint server for biology

    2023  

    Abstract: After endocytosis, many plasma membrane components are recycled via narrow-diameter membrane tubules that emerge from early endosomes to form recycling endosomes, eventually leading to their return to the plasma membrane. We previously showed that the F- ... ...

    Abstract After endocytosis, many plasma membrane components are recycled via narrow-diameter membrane tubules that emerge from early endosomes to form recycling endosomes, eventually leading to their return to the plasma membrane. We previously showed that the F-BAR and SH3 domain Syndapin/PACSIN-family protein SDPN-1 is required
    Language English
    Publishing date 2023-02-28
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.27.530328
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Role of Exosomes in Lysosomal Storage Disorders.

    Gleason, Adenrele M / Woo, Elizabeth G / McKinney, Cindy / Sidransky, Ellen

    Biomolecules

    2021  Volume 11, Issue 4

    Abstract: Exosomes, small membrane-bound organelles formed from endosomal membranes, represent a heterogenous source of biological and pathological biomarkers capturing the metabolic status of a cell. Exosomal cargo, including lipids, proteins, mRNAs, and miRNAs, ... ...

    Abstract Exosomes, small membrane-bound organelles formed from endosomal membranes, represent a heterogenous source of biological and pathological biomarkers capturing the metabolic status of a cell. Exosomal cargo, including lipids, proteins, mRNAs, and miRNAs, can either act as inter-cellular messengers or are shuttled for autophagic/lysosomal degradation. Most cell types in the central nervous system (CNS) release exosomes, which serve as long and short distance communicators between neurons, astrocytes, oligodendrocytes, and microglia. Lysosomal storage disorders are diseases characterized by the accumulation of partially or undigested cellular waste. The exosomal content in these diseases is intrinsic to each individual disorder. Emerging research indicates that lysosomal dysfunction enhances exocytosis, and hence, in lysosomal disorders, exosomal secretion may play a role in disease pathogenesis. Furthermore, the unique properties of exosomes and their ability to carry cargo between adjacent cells and organs, and across the blood-brain barrier, make them attractive candidates for use as therapeutic delivery vehicles. Thus, understanding exosomal content and function may have utility in the treatment of specific lysosomal storage disorders. Since lysosomal dysfunction and the deficiency of at least one lysosomal enzyme, glucocerebrosidase, is associated with the development of parkinsonism, the study and use of exosomes may contribute to an improved understanding of Parkinson disease, potentially leading to new therapeutics.
    Language English
    Publishing date 2021-04-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom11040576
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The D409H variant in GBA1: Challenges in predicting the Gaucher phenotype in the newborn screening era.

    Gleason, Adenrele M / D'Souza, Andrea / Ryan, Emory / Grochowsky, Angela R / Carter, Camille R / Goker-Alpan, Ozlem / Lopez, Grisel / Tayebi, Nahid / Sidransky, Ellen

    American journal of medical genetics. Part A

    2023  Volume 191, Issue 7, Page(s) 1783–1791

    Abstract: Gaucher disease (GD) is an autosomal recessive disorder resulting from glucocerebrosidase deficiency due to pathologic variants in GBA1. While clinically heterogeneous, GD encompasses three types, non-neuronopathic (GD1), acute neuronopathic (GD2), and ... ...

    Abstract Gaucher disease (GD) is an autosomal recessive disorder resulting from glucocerebrosidase deficiency due to pathologic variants in GBA1. While clinically heterogeneous, GD encompasses three types, non-neuronopathic (GD1), acute neuronopathic (GD2), and chronic neuronopathic (GD3). Newborn screening (NBS), which has made remarkable inroads in detecting certain diseases before detrimental health consequences and fatality ensues, is now being piloted for GD in several states and countries. Early on, clinical features of GD2 can overlap with GD3; hence, predicting outcome is challenging. As NBS for GD becomes more available, the increased detection of GD in neonates is inevitable. As a result, health care providers and families will be faced with uncertainty with respect to clinical management. Since more severe GBA1 variants are generally associated with neuronopathic GD, there has been an increased dependence on genotypic information. We present an infant detected by NBS with genotype D409H(p.Asp448His)/RecNciI (p.Leu483Pro; p.Ala495Pro;p.Val499=). To assist in genetic counseling, we performed a retrospective review of other patients in our cohort carrying D409H and reviewed the literature. The study illustrates the challenges faced in counseling for infants with neuronopathic GD, even with known GBA1 variants, and the tough management decisions that can ensue from detection in newborns.
    MeSH term(s) Humans ; Infant, Newborn ; Glucosylceramidase/genetics ; Neonatal Screening ; Gaucher Disease/diagnosis ; Gaucher Disease/genetics ; Phenotype ; Genotype
    Chemical Substances Glucosylceramidase (EC 3.2.1.45)
    Language English
    Publishing date 2023-04-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2108614-X
    ISSN 1552-4833 ; 0148-7299 ; 1552-4825
    ISSN (online) 1552-4833
    ISSN 0148-7299 ; 1552-4825
    DOI 10.1002/ajmg.a.63202
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1376/A: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  6. Article ; Online: Syndapin/SDPN-1 is required for endocytic recycling and endosomal actin association in the C. elegans intestine.

    Gleason, Adenrele M / Nguyen, Ken C Q / Hall, David H / Grant, Barth D

    Molecular biology of the cell

    2016  

    Abstract: Syndapin/Pascin family F-BAR domain proteins bind directly to membrane lipids and are associated with actin dynamics at the plasma membrane. Previous reports have also implicated mammalian syndapin 2 in endosome function during receptor recycling, but ... ...

    Abstract Syndapin/Pascin family F-BAR domain proteins bind directly to membrane lipids and are associated with actin dynamics at the plasma membrane. Previous reports have also implicated mammalian syndapin 2 in endosome function during receptor recycling, but precise analysis of a putative recycling function for syndapin in mammalian systems is difficult because of syndapin effects on the earlier step of endocytic uptake, and potential redundancy among the three separate genes that encode mammalian syndapin isoforms. Here we analyze the endocytic transport function of the only C. elegans syndapin, SDPN-1. We find that SDPN-1 is a resident protein of the early and basolateral recycling endosomes in the C. elegans intestinal epithelium, and sdpn-1 deletion mutants display phenotypes indicating a block in basolateral recycling transport. sdpn-1 mutants accumulate abnormal endosomes positive for early endosome and recycling endosome markers that are normally separate, and such endosomes accumulate high levels of basolateral recycling cargo. Furthermore, we observed strong colocalization of endosomal SDPN-1 with the F-actin biosensor Lifeact, and found that loss of SDPN-1 greatly reduced Lifeact accumulation on early endosomes. Taken together our results provide strong evidence for an in vivo function of syndapin in endocytic recycling, and suggest that syndapin promotes transport via endosomal fission.
    Language English
    Publishing date 2016-09-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E16-02-0116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2853: Show issues Location:
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    Zs.MO 410: Show issues

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