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  1. Article ; Online: Divergent mechanisms of inflammasome activation in neutrophil early response and inflammation.

    Catz, Sergio D

    Nature immunology

    2023  Volume 24, Issue 12, Page(s) 1970–1971

    MeSH term(s) Humans ; Inflammasomes ; Neutrophils ; Inflammation ; NLR Family, Pyrin Domain-Containing 3 Protein ; Interleukin-1beta
    Chemical Substances Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; Interleukin-1beta
    Language English
    Publishing date 2023-10-31
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-023-01684-x
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    Zs.A 5294: Show issues Location:
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  2. Article ; Online: Editorial: The secrets of secretion.

    Catz, Sergio D

    Journal of leukocyte biology

    2017  Volume 102, Issue 1, Page(s) 4–6

    MeSH term(s) Animals ; Exocytosis/physiology ; Humans ; Neutrophil Activation ; Secretory Vesicles/secretion ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Tumor Necrosis Factor-alpha
    Language English
    Publishing date 2017-06-27
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1189/jlb.3CE0217-046R
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  3. Article ; Online: The role of Rab27a in the regulation of neutrophil function.

    Catz, Sergio D

    Cellular microbiology

    2014  Volume 16, Issue 9, Page(s) 1301–1310

    Abstract: Neutrophils are central regulators of the innate immune response and help shape the adaptive immune response. Malfunction and unregulated neutrophil activation leads to disease and inflammation. During the host response to infection, neutrophils display ... ...

    Abstract Neutrophils are central regulators of the innate immune response and help shape the adaptive immune response. Malfunction and unregulated neutrophil activation leads to disease and inflammation. During the host response to infection, neutrophils display several mechanisms of defense mediated by their arsenal of granular proteins. Regulation of granular trafficking, docking and fusion is at the core of the neutrophil defense response to pathogens. The small GTPase Rab27a has emerged as a central regulator of the neutrophil response through its tight control of vesicular trafficking and degranulation. This review focuses on the latest research that has led to the characterization of Rab27a as an essential regulator of neutrophil function.
    MeSH term(s) Animals ; Exocytosis/physiology ; Humans ; NADPH Oxidases/metabolism ; Neutrophils/metabolism ; Secretory Vesicles/metabolism ; rab GTP-Binding Proteins/metabolism ; rab27 GTP-Binding Proteins
    Chemical Substances rab27 GTP-Binding Proteins ; NADPH Oxidases (EC 1.6.3.-) ; RAB27A protein, human (EC 3.6.1.-.) ; rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2014-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1468320-9
    ISSN 1462-5822 ; 1462-5814
    ISSN (online) 1462-5822
    ISSN 1462-5814
    DOI 10.1111/cmi.12328
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    Zs.A 5288: Show issues Location:
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  4. Article ; Online: Therapeutic targeting of neutrophil exocytosis.

    Catz, Sergio D / McLeish, Kenneth R

    Journal of leukocyte biology

    2020  Volume 107, Issue 3, Page(s) 393–408

    Abstract: Dysregulation of neutrophil activation causes disease in humans. Neither global inhibition of neutrophil functions nor neutrophil depletion provides safe and/or effective therapeutic approaches. The role of neutrophil granule exocytosis in multiple steps ...

    Abstract Dysregulation of neutrophil activation causes disease in humans. Neither global inhibition of neutrophil functions nor neutrophil depletion provides safe and/or effective therapeutic approaches. The role of neutrophil granule exocytosis in multiple steps leading to recruitment and cell injury led each of our laboratories to develop molecular inhibitors that interfere with specific molecular regulators of secretion. This review summarizes neutrophil granule formation and contents, the role granule cargo plays in neutrophil functional responses and neutrophil-mediated diseases, and the mechanisms of granule release that provide the rationale for development of our exocytosis inhibitors. We present evidence for the inhibition of granule exocytosis in vitro and in vivo by those inhibitors and summarize animal data indicating that inhibition of neutrophil exocytosis is a viable therapeutic strategy.
    MeSH term(s) Animals ; Cytoplasmic Granules/metabolism ; Disease ; Exocytosis ; Humans ; Molecular Targeted Therapy ; Neutrophils/cytology ; SNARE Proteins/metabolism
    Chemical Substances SNARE Proteins
    Language English
    Publishing date 2020-01-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1002/JLB.3RI0120-645R
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  5. Article ; Online: Super-Resolution Microscopy and Particle-Tracking Approaches for the Study of Vesicular Trafficking in Primary Neutrophils.

    Johnson, Jennifer L / Pestonjamasp, Kersi / Kiosses, William B / Catz, Sergio D

    Methods in molecular biology (Clifton, N.J.)

    2020  Volume 2233, Page(s) 193–202

    Abstract: Neutrophils are short-lived cells after isolation. The analysis of neutrophil vesicular trafficking requires rapid and gentle handling. Recently developed super-resolution microscopy technologies have generated unparalleled opportunities to help ... ...

    Abstract Neutrophils are short-lived cells after isolation. The analysis of neutrophil vesicular trafficking requires rapid and gentle handling. Recently developed super-resolution microscopy technologies have generated unparalleled opportunities to help understand the molecular mechanisms regulating neutrophil vesicular trafficking, exocytosis, and associated functions at the molecular level. Here, we describe super-resolution and total internal reflection fluorescence (TIRF) microscopy approaches for the analysis of vesicular trafficking and associated functions of primary neutrophils.
    MeSH term(s) Cell Movement/genetics ; Exocytosis/genetics ; Humans ; Microscopy, Fluorescence/methods ; Neutrophils/metabolism ; Neutrophils/ultrastructure ; Primary Cell Culture/methods ; Protein Transport/genetics ; rab GTP-Binding Proteins/genetics
    Chemical Substances rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2020-09-30
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-1044-2_13
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  6. Article ; Online: Molecular mechanisms regulating secretory organelles and endosomes in neutrophils and their implications for inflammation.

    Ramadass, Mahalakshmi / Catz, Sergio D

    Immunological reviews

    2016  Volume 273, Issue 1, Page(s) 249–265

    Abstract: Neutrophils constitute the first line of cellular defense against invading microorganisms and modulate the subsequent innate and adaptive immune responses. In order to execute a rapid and precise response to infections, neutrophils rely on preformed ... ...

    Abstract Neutrophils constitute the first line of cellular defense against invading microorganisms and modulate the subsequent innate and adaptive immune responses. In order to execute a rapid and precise response to infections, neutrophils rely on preformed effector molecules stored in a variety of intracellular granules. Neutrophil granules contain microbicidal factors, the membrane-bound components of the respiratory burst oxidase, membrane-bound adhesion molecules, and receptors that facilitate the execution of all neutrophil functions including adhesion, transmigration, phagocytosis, degranulation, and neutrophil extracellular trap formation. The rapid mobilization of intracellular organelles is regulated by vesicular trafficking mechanisms controlled by effector molecules that include small GTPases and their interacting proteins. In this review, we focus on recent discoveries of mechanistic processes that are at center stage of the regulation of neutrophil function, highlighting the discrete and selective pathways controlled by trafficking modulators. In particular, we describe novel pathways controlled by the Rab27a effectors JFC1 and Munc13-4 in the regulation of degranulation, reactive oxygen species and neutrophil extracellular trap production, and endolysosomal signaling. Finally, we discuss the importance of understanding these molecular mechanisms in order to design novel approaches to modulate neutrophil-mediated inflammatory processes in a targeted fashion.
    MeSH term(s) Animals ; Cell Degranulation ; Endosomes/metabolism ; Humans ; Inflammation/immunology ; Membrane Proteins/metabolism ; Neutrophils/physiology ; Phagocytosis ; Protein Transport ; Secretory Vesicles/metabolism ; rab GTP-Binding Proteins/metabolism ; rab27 GTP-Binding Proteins
    Chemical Substances Membrane Proteins ; SYTL1 protein, human ; UNC13D protein, human ; rab27 GTP-Binding Proteins ; RAB27A protein, human (EC 3.6.1.-.) ; rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2016-08-03
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/imr.12452
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    Se 160: Show issues Location:
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  7. Article ; Online: Noncanonical Hippo Signalling in the Regulation of Leukocyte Function.

    Kurz, Angela R M / Catz, Sergio D / Sperandio, Markus

    Trends in immunology

    2018  Volume 39, Issue 8, Page(s) 656–669

    Abstract: The mammalian sterile 20-like (MST) kinases are central constituents of the evolutionary ancient canonical Hippo pathway regulating cell proliferation and survival. However, perhaps surprisingly, MST1 deficiency in human patients leads to a severe ... ...

    Abstract The mammalian sterile 20-like (MST) kinases are central constituents of the evolutionary ancient canonical Hippo pathway regulating cell proliferation and survival. However, perhaps surprisingly, MST1 deficiency in human patients leads to a severe combined immunodeficiency syndrome with features of autoimmune disease. In line with this, Mst1-deficient mice exhibit severe defects in lymphocyte and neutrophil functions as well as disturbed intracellular vesicle transport. These findings spurred research on the noncanonical functions of MST1 in leukocytes. Here, we summarise the latest findings on this topic and discuss MST1 as a critical regulator of various leukocyte functions.
    MeSH term(s) Animals ; Autoimmune Diseases/genetics ; Biological Evolution ; Humans ; Leukocytes/metabolism ; MAP Kinase Kinase Kinases/genetics ; MAP Kinase Kinase Kinases/metabolism ; Mice ; Protein-Serine-Threonine Kinases/metabolism ; Severe Combined Immunodeficiency/genetics ; Signal Transduction
    Chemical Substances Hippo protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; MAP Kinase Kinase Kinases (EC 2.7.11.25) ; MAP3K10 protein, human (EC 2.7.11.25)
    Language English
    Publishing date 2018-06-26
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2036831-8
    ISSN 1471-4981 ; 1471-4906
    ISSN (online) 1471-4981
    ISSN 1471-4906
    DOI 10.1016/j.it.2018.05.003
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    Zs.A 1601: Show issues Location:
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    Zs.MG 2: Show issues

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  8. Article: Characterization of Rab27a and JFC1 as constituents of the secretory machinery of prostate-specific antigen in prostate carcinoma cells.

    Catz, Sergio D

    Methods in enzymology

    2008  Volume 438, Page(s) 25–40

    Abstract: Prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) are produced by prostate carcinoma cells. Their secretion has implications in both prostate cancer diagnosis and progression. The mechanisms involved in PSA and PSAP secretion ... ...

    Abstract Prostate-specific antigen (PSA) and prostate-specific acid phosphatase (PSAP) are produced by prostate carcinoma cells. Their secretion has implications in both prostate cancer diagnosis and progression. The mechanisms involved in PSA and PSAP secretion in response to androgens have remained relatively unknown. The small GTPase Rab27a regulates exocytosis in several tissues. Here, we present methods for the characterization of Rab27a and its effector JFC1/Slp1 as key components of the secretory machinery that regulates exocytosis in prostate carcinoma cells.
    MeSH term(s) Acid Phosphatase ; Cell Line, Tumor ; Down-Regulation ; Exocytosis ; Humans ; Male ; Membrane Proteins/metabolism ; Permeability ; Prostate-Specific Antigen/metabolism ; Prostatic Neoplasms/metabolism ; Protein Interaction Mapping/methods ; Protein Structure, Tertiary ; Protein Transport/physiology ; Protein Tyrosine Phosphatases/metabolism ; RNA, Small Interfering/pharmacology ; Vesicular Transport Proteins ; rab GTP-Binding Proteins/metabolism ; rab27 GTP-Binding Proteins
    Chemical Substances Membrane Proteins ; RNA, Small Interfering ; SYTL1 protein, human ; Sytl1 protein, mouse ; Vesicular Transport Proteins ; rab27 GTP-Binding Proteins ; Acid Phosphatase (EC 3.1.3.2) ; prostatic acid phosphatase (EC 3.1.3.2) ; Protein Tyrosine Phosphatases (EC 3.1.3.48) ; Prostate-Specific Antigen (EC 3.4.21.77) ; RAB27A protein, human (EC 3.6.1.-.) ; rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2008-04-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 0076-6879
    ISSN 0076-6879
    DOI 10.1016/S0076-6879(07)38003-8
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  9. Article ; Online: DYNC1LI2 regulates localization of the chaperone-mediated autophagy receptor LAMP2A and improves cellular homeostasis in cystinosis.

    Rahman, Farhana / Johnson, Jennifer L / Zhang, Jinzhong / He, Jing / Pestonjamasp, Kersi / Cherqui, Stephanie / Catz, Sergio D

    Autophagy

    2021  Volume 18, Issue 5, Page(s) 1108–1126

    Abstract: The dynein motor protein complex is required for retrograde transport but the functions of the intermediate-light chains that form the cargo-binding complex are not elucidated and the importance of individual subunits in maintaining cellular homeostasis ... ...

    Abstract The dynein motor protein complex is required for retrograde transport but the functions of the intermediate-light chains that form the cargo-binding complex are not elucidated and the importance of individual subunits in maintaining cellular homeostasis is unknown. Here, using mRNA arrays and protein analysis, we show that the dynein subunit, DYNC1LI2 (dynein, cytoplasmic 1 light intermediate chain 2) is downregulated in cystinosis, a lysosomal storage disorder caused by genetic defects in CTNS (cystinosin, lysosomal cystine transporter). Reconstitution of DYNC1LI2 expression in
    MeSH term(s) Autophagy ; Chaperone-Mediated Autophagy ; Cystine/metabolism ; Cystinosis/genetics ; Cystinosis/metabolism ; Cytoplasmic Dyneins/genetics ; Cytoplasmic Dyneins/metabolism ; Homeostasis ; Humans ; Low Density Lipoprotein Receptor-Related Protein-2/metabolism ; Lysosomal-Associated Membrane Protein 2/genetics ; Lysosomal-Associated Membrane Protein 2/metabolism ; Lysosomes/metabolism
    Chemical Substances LAMP2 protein, human ; Low Density Lipoprotein Receptor-Related Protein-2 ; Lysosomal-Associated Membrane Protein 2 ; Cystine (48TCX9A1VT) ; Cytoplasmic Dyneins (EC 3.6.4.2) ; DYNC1LI2 protein, human (EC 3.6.4.2)
    Language English
    Publishing date 2021-10-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2021.1971937
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    Zs.A 6741: Show issues Location:
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  10. Article ; Online: Rab27a regulates GM-CSF-dependent priming of neutrophil exocytosis.

    Ramadass, Mahalakshmi / Johnson, Jennifer Linda / Catz, Sergio D

    Journal of leukocyte biology

    2016  Volume 101, Issue 3, Page(s) 693–702

    Abstract: Neutrophil secretory proteins are mediators of systemic inflammation in infection, trauma, and cancer. In response to specific inflammatory mediators, neutrophil granules are mobilized and cargo proteins released to modulate the microenvironment of ... ...

    Abstract Neutrophil secretory proteins are mediators of systemic inflammation in infection, trauma, and cancer. In response to specific inflammatory mediators, neutrophil granules are mobilized and cargo proteins released to modulate the microenvironment of inflammatory sites and tumors. In particular, GM-CSF, a cytokine secreted by several immune, nonimmune, and tumor cells, regulates neutrophil priming and exocytosis. Whereas a comprehensive understanding of this process is necessary to design appropriate anti-inflammatory therapies, the molecular effectors regulating GM-CSF-dependent priming of neutrophil exocytosis are currently unknown. With the use of neutrophils deficient in the small GTPase Rab27a or its effector Munc13-4, we show that although both of these secretory factors control matrix metalloproteinase-9 (MMP-9) and myeloperoxidase (MPO) exocytosis in response to GM-CSF, their involvement in exocytosis after GM-CSF priming is very different. Whereas GM-CSF priming-induced exocytosis is abolished in the absence of Rab27a for all secondary stimuli tested, including TLR7, TLR9, and formyl peptide receptor 1 (Fpr1) ligands, cells lacking Munc13-4 showed a significant exocytic response to GM-CSF priming. The mobilization of CD11b was independent of both Rab27a and Munc13-4 in GM-CSF-primed cells unless the cells were stimulated with nucleic acid-sensing TLR ligand, thus highlighting a role for both Rab27a and Munc13-4 in endocytic TLR maturation. Finally, the observation that the absence of Rab27a expression impairs the exocytosis of MMP-9 and MPO under both primed and unprimed conditions suggests that Rab27a is a possible target for intervention in inflammatory processes in which GM-CSF-dependent neutrophil priming is involved.
    MeSH term(s) Animals ; Endocytosis/drug effects ; Exocytosis/drug effects ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Matrix Metalloproteinase 9/metabolism ; Mice ; Mice, Inbred C57BL ; Neutrophils/cytology ; Neutrophils/drug effects ; Neutrophils/metabolism ; Peroxidase/metabolism ; Toll-Like Receptor 9/agonists ; Toll-Like Receptor 9/metabolism ; Up-Regulation/drug effects ; Vesicular Transport Proteins/metabolism ; rab GTP-Binding Proteins/metabolism ; rab27 GTP-Binding Proteins
    Chemical Substances Toll-Like Receptor 9 ; Vesicular Transport Proteins ; rab27 GTP-Binding Proteins ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1) ; Peroxidase (EC 1.11.1.7) ; Matrix Metalloproteinase 9 (EC 3.4.24.35) ; Rab27a protein, mouse (EC 3.6.1.-.) ; rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2016-10-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1189/jlb.3AB0416-189RR
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