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  1. Article: SGIP1 in axons prevents internalization of desensitized CB1R and modifies its function.

    Durydivka, Oleh / Mackie, Ken / Blahos, Jaroslav

    Frontiers in neuroscience

    2023  Volume 17, Page(s) 1213094

    Abstract: In the central nervous system (CNS), cannabinoid receptor 1 (CB1R) is preferentially expressed in axons where it has a unique property, namely resistance to agonist-driven endocytosis. This review aims to summarize what we know about molecular mechanisms ...

    Abstract In the central nervous system (CNS), cannabinoid receptor 1 (CB1R) is preferentially expressed in axons where it has a unique property, namely resistance to agonist-driven endocytosis. This review aims to summarize what we know about molecular mechanisms of CB1R cell surface stability in axonal compartments, how these impact CB1R signaling, and to consider their physiological consequences. This review then focuses on a potential candidate for maintaining axonal CB1R at the cell surface, Src homology 3-domain growth factor receptor-bound 2-like endophilin interacting protein 1 (SGIP1). SGIP1 may contribute to the polarized distribution of CB1R and modify its signaling in axons. In addition, deletion of SGIP1 results in discrete behavioral changes in modalities controlled by the endocannabinoid system
    Language English
    Publishing date 2023-07-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2023.1213094
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Hexahydrocannabinol (HHC) and Δ

    Durydivka, Oleh / Palivec, Petr / Gazdarica, Matej / Mackie, Ken / Blahos, Jaroslav / Kuchar, Martin

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 9181

    Abstract: The Cannabis sativa plant has been used for centuries as a recreational drug and more recently in the treatment of patients with neurological or psychiatric disorders. In many instances, treatment goals include relief from posttraumatic disorders, ... ...

    Abstract The Cannabis sativa plant has been used for centuries as a recreational drug and more recently in the treatment of patients with neurological or psychiatric disorders. In many instances, treatment goals include relief from posttraumatic disorders, anxiety, or to support treatment of chronic pain. Ligands acting on cannabinoid receptor 1 (CB1R) are also potential targets for the treatment of other health conditions. Using an evidence-based approach, pharmacological investigation of CB1R agonists is timely, with the aim to provide chronically ill patients relief using well-defined and characterized compounds from cannabis. Hexahydrocannabinol (HHC), currently available over the counter in many countries to adults and even children, is of great interests to policy makers, legal administrators, and healthcare regulators, as well as pharmacologists. Herein, we studied the pharmacodynamics of HHC epimers, which activate CB1R. We compared their key CB1R-mediated signaling pathway activities and compared them to the pathways activated by Δ
    MeSH term(s) Dronabinol/pharmacology ; Receptor, Cannabinoid, CB1/metabolism ; Receptor, Cannabinoid, CB1/agonists ; Signal Transduction/drug effects ; Humans ; Cannabinol/pharmacology ; Animals ; Cannabinoid Receptor Agonists/pharmacology ; HEK293 Cells ; Mice
    Chemical Substances Dronabinol (7J8897W37S) ; Receptor, Cannabinoid, CB1 ; Cannabinol (7UYP6MC9GH) ; Cannabinoid Receptor Agonists
    Language English
    Publishing date 2024-04-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-58845-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Multiple Sgip1 splice variants inhibit cannabinoid receptor 1 internalization.

    Durydivka, Oleh / Gazdarica, Matej / Vecerkova, Katerina / Radenkovic, Silvia / Blahos, Jaroslav

    Gene

    2023  Volume 892, Page(s) 147851

    Abstract: Alternative splicing can often result in the expression of distinct protein isoforms from a single gene, with specific composition and properties. SH3-containing GRB2-like protein 3-interacting protein 1 (Sgip1) is a brain-enriched protein that regulates ...

    Abstract Alternative splicing can often result in the expression of distinct protein isoforms from a single gene, with specific composition and properties. SH3-containing GRB2-like protein 3-interacting protein 1 (Sgip1) is a brain-enriched protein that regulates clathrin-mediated endocytosis and interferes with the internalization of cannabinoid receptor 1. Several research groups have studied the physiological importance of Sgip1, and four Sgip1 protein isoforms have been described to date, while the NCBI Gene database predicts the expression of 20 splice variants from the Sgip1 gene in mice. In this work, we cloned 15 Sgip1 splice variants from the mouse brain, including 11 novel splice variants. The cloned splice variants differed in exon composition within two Sgip1 regions: the membrane phospholipid-binding domain and the proline-rich region. All the Sgip1 splice isoforms had similar stability and comparable ability to inhibit the internalization of cannabinoid receptor 1. None of the isoforms influenced the internalization of the µ-opioid receptor. We confirm the expression of Sgip1 splice variants described in previous studies or predicted in silico. Our data provide a basis for further studies exploring the significance of Sgip1 splicing, and we suggest a new classification of Sgip1 splice variants to unify their nomenclature.
    MeSH term(s) Animals ; Mice ; Alternative Splicing ; Endocytosis/genetics ; Exons ; Protein Isoforms/genetics ; Receptors, Cannabinoid/genetics
    Chemical Substances Protein Isoforms ; Receptors, Cannabinoid ; CNR1 protein, mouse ; SGIP1 protein, mouse
    Language English
    Publishing date 2023-09-30
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 391792-7
    ISSN 1879-0038 ; 0378-1119
    ISSN (online) 1879-0038
    ISSN 0378-1119
    DOI 10.1016/j.gene.2023.147851
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: SGIP1 modulates kinetics and interactions of the cannabinoid receptor 1 and G protein-coupled receptor kinase 3 signalosome.

    Gazdarica, Matej / Noda, Judith / Durydivka, Oleh / Novosadova, Vendula / Mackie, Ken / Pin, Jean-Philippe / Prezeau, Laurent / Blahos, Jaroslav

    Journal of neurochemistry

    2022  Volume 160, Issue 6, Page(s) 625–642

    Abstract: Cannabinoid receptor 1 (CB1R), a G protein-coupled receptor, plays a fundamental role in synaptic plasticity. Abnormal activity and deregulation of CB1R signaling result in a broad spectrum of pathological conditions. CB1R signaling is regulated by ... ...

    Abstract Cannabinoid receptor 1 (CB1R), a G protein-coupled receptor, plays a fundamental role in synaptic plasticity. Abnormal activity and deregulation of CB1R signaling result in a broad spectrum of pathological conditions. CB1R signaling is regulated by receptor desensitization including phosphorylation of residues within the intracellular C terminus by G protein-coupled receptor kinases (GRKs) that may lead to endocytosis. Furthermore, CB1R signaling is regulated by the protein Src homology 3-domain growth factor receptor-bound 2-like (SGIP1) that hinders receptor internalization, while enhancing CB1R association with β-arrestin. It has been postulated that phosphorylation of two clusters of serine/threonine residues,
    MeSH term(s) Carrier Proteins/metabolism ; GTP-Binding Proteins ; Kinetics ; Phosphorylation ; Receptors, Cannabinoid/metabolism ; Serine/metabolism ; Threonine/metabolism
    Chemical Substances Carrier Proteins ; Receptors, Cannabinoid ; Threonine (2ZD004190S) ; Serine (452VLY9402) ; GTP-Binding Proteins (EC 3.6.1.-)
    Language English
    Publishing date 2022-01-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80158-6
    ISSN 1471-4159 ; 0022-3042 ; 1474-1644
    ISSN (online) 1471-4159
    ISSN 0022-3042 ; 1474-1644
    DOI 10.1111/jnc.15569
    Database MEDical Literature Analysis and Retrieval System OnLINE

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