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  1. Article: A voyage from the ER: spatiotemporal insights into polarized protein secretion in neurons.

    Kersten, Noortje / Farías, Ginny G

    Frontiers in cell and developmental biology

    2023  Volume 11, Page(s) 1333738

    Abstract: To function properly, neurons must maintain a proteome that differs in their somatodendritic and axonal domain. This requires the polarized sorting of newly synthesized secretory and transmembrane proteins into different vesicle populations as they ... ...

    Abstract To function properly, neurons must maintain a proteome that differs in their somatodendritic and axonal domain. This requires the polarized sorting of newly synthesized secretory and transmembrane proteins into different vesicle populations as they traverse the secretory pathway. Although the trans-Golgi-network is generally considered to be the main sorting hub, this sorting process may already begin at the ER and continue through the Golgi cisternae. At each step in the sorting process, specificity is conferred by adaptors, GTPases, tethers, and SNAREs. Besides this, local synthesis and unconventional protein secretion may contribute to the polarized proteome to enable rapid responses to stimuli. For some transmembrane proteins, some of the steps in the sorting process are well-studied. These will be highlighted here. The universal rules that govern polarized protein sorting remain unresolved, therefore we emphasize the need to approach this problem in an unbiased, top-down manner. Unraveling these rules will contribute to our understanding of neuronal development and function in health and disease.
    Language English
    Publishing date 2023-12-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2023.1333738
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Endoplasmic reticulum - condensate interactions in protein synthesis and secretion.

    Nguyen, Dan T M / Koppers, Max / Farías, Ginny G

    Current opinion in cell biology

    2024  Volume 88, Page(s) 102357

    Abstract: In the past decade, a growing amount of evidence has demonstrated that organelles do not act autonomously and independently but rather communicate with each other to coordinate different processes for proper cellular function. With a highly extended ... ...

    Abstract In the past decade, a growing amount of evidence has demonstrated that organelles do not act autonomously and independently but rather communicate with each other to coordinate different processes for proper cellular function. With a highly extended network throughout the cell, the endoplasmic reticulum (ER) plays a central role in interorganelle communication through membrane contact sites. Here, we highlight recent evidence indicating that the ER also forms contacts with membrane-less organelles. These interactions contribute to the dynamic assembly and disassembly of condensates and controlled protein secretion. Additionally, emerging evidence suggests their involvement in mRNA localization and localized translation. We further explore exciting future directions of this emerging theme in the organelle contact site field.
    Language English
    Publishing date 2024-04-15
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1026381-0
    ISSN 1879-0410 ; 0955-0674
    ISSN (online) 1879-0410
    ISSN 0955-0674
    DOI 10.1016/j.ceb.2024.102357
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A voyage from the ER

    Noortje Kersten / Ginny G. Farías

    Frontiers in Cell and Developmental Biology, Vol

    spatiotemporal insights into polarized protein secretion in neurons

    2023  Volume 11

    Abstract: To function properly, neurons must maintain a proteome that differs in their somatodendritic and axonal domain. This requires the polarized sorting of newly synthesized secretory and transmembrane proteins into different vesicle populations as they ... ...

    Abstract To function properly, neurons must maintain a proteome that differs in their somatodendritic and axonal domain. This requires the polarized sorting of newly synthesized secretory and transmembrane proteins into different vesicle populations as they traverse the secretory pathway. Although the trans-Golgi-network is generally considered to be the main sorting hub, this sorting process may already begin at the ER and continue through the Golgi cisternae. At each step in the sorting process, specificity is conferred by adaptors, GTPases, tethers, and SNAREs. Besides this, local synthesis and unconventional protein secretion may contribute to the polarized proteome to enable rapid responses to stimuli. For some transmembrane proteins, some of the steps in the sorting process are well-studied. These will be highlighted here. The universal rules that govern polarized protein sorting remain unresolved, therefore we emphasize the need to approach this problem in an unbiased, top-down manner. Unraveling these rules will contribute to our understanding of neuronal development and function in health and disease.
    Keywords neurons ; polarized protein sorting ; endoplasmic reticulum ; ERES ; Golgi apparatus ; conventional protein secretion ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Moving the ER tip by tip.

    Nguyen, Ha H / Farías, Ginny G

    Developmental cell

    2021  Volume 56, Issue 24, Page(s) 3305–3306

    Abstract: Endoplasmic reticulum (ER) and microtubule (MT) interactions have been observed in different cell types. However, how these interactions are regulated remains unknown. In this issue of Developmental Cell, Nourbakhsh et al. show that an ER-localized ... ...

    Abstract Endoplasmic reticulum (ER) and microtubule (MT) interactions have been observed in different cell types. However, how these interactions are regulated remains unknown. In this issue of Developmental Cell, Nourbakhsh et al. show that an ER-localized kinase, TAOK2, catalyzes the dynamic tethering of the ER tip to the MT tip.
    MeSH term(s) Endoplasmic Reticulum ; Microtubules
    Language English
    Publishing date 2021-12-21
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2021.12.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Organelle distribution in neurons: Logistics behind polarized transport.

    Koppers, Max / Farías, Ginny G

    Current opinion in cell biology

    2021  Volume 71, Page(s) 46–54

    Abstract: Highly polarized neurons need to carefully regulate the distribution of organelles and other cargoes into their two morphologically and functionally distinct domains, the somatodendritic and axonal compartments, to maintain proper neuron homeostasis. An ... ...

    Abstract Highly polarized neurons need to carefully regulate the distribution of organelles and other cargoes into their two morphologically and functionally distinct domains, the somatodendritic and axonal compartments, to maintain proper neuron homeostasis. An outstanding question in the field is how organelles reach their correct destination. Long-range transport along microtubules, driven by motors, ensures a fast and controlled availability of organelles in axons and dendrites, but it remains largely unclear what rules govern their transport into the correct compartment. Here, we review the emerging concepts of polarized cargo trafficking in neurons, highlighting the role of microtubule organization, microtubule-associated proteins, and motor proteins and discuss compartment-specific inclusion and exclusion mechanisms as well as the regulation of correct coupling of cargoes to motor proteins.
    MeSH term(s) Axons ; Dendrites ; Kinesin ; Microtubules ; Neurons ; Organelles
    Chemical Substances Kinesin (EC 3.6.4.4)
    Language English
    Publishing date 2021-03-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1026381-0
    ISSN 1879-0410 ; 0955-0674
    ISSN (online) 1879-0410
    ISSN 0955-0674
    DOI 10.1016/j.ceb.2021.02.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Complex Interactions Between Membrane-Bound Organelles, Biomolecular Condensates and the Cytoskeleton.

    Koppers, Max / Özkan, Nazmiye / Farías, Ginny G

    Frontiers in cell and developmental biology

    2020  Volume 8, Page(s) 618733

    Abstract: Membrane-bound and membraneless organelles/biomolecular condensates ensure compartmentalization into functionally distinct units enabling proper organization of cellular processes. Membrane-bound organelles form dynamic contacts with each other to enable ...

    Abstract Membrane-bound and membraneless organelles/biomolecular condensates ensure compartmentalization into functionally distinct units enabling proper organization of cellular processes. Membrane-bound organelles form dynamic contacts with each other to enable the exchange of molecules and to regulate organelle division and positioning in coordination with the cytoskeleton. Crosstalk between the cytoskeleton and dynamic membrane-bound organelles has more recently also been found to regulate cytoskeletal organization. Interestingly, recent work has revealed that, in addition, the cytoskeleton and membrane-bound organelles interact with cytoplasmic biomolecular condensates. The extent and relevance of these complex interactions are just beginning to emerge but may be important for cytoskeletal organization and organelle transport and remodeling. In this review, we highlight these emerging functions and emphasize the complex interplay of the cytoskeleton with these organelles. The crosstalk between membrane-bound organelles, biomolecular condensates and the cytoskeleton in highly polarized cells such as neurons could play essential roles in neuronal development, function and maintenance.
    Language English
    Publishing date 2020-12-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2020.618733
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  7. Article ; Online: Complex Interactions Between Membrane-Bound Organelles, Biomolecular Condensates and the Cytoskeleton

    Max Koppers / Nazmiye Özkan / Ginny G. Farías

    Frontiers in Cell and Developmental Biology, Vol

    2020  Volume 8

    Abstract: Membrane-bound and membraneless organelles/biomolecular condensates ensure compartmentalization into functionally distinct units enabling proper organization of cellular processes. Membrane-bound organelles form dynamic contacts with each other to enable ...

    Abstract Membrane-bound and membraneless organelles/biomolecular condensates ensure compartmentalization into functionally distinct units enabling proper organization of cellular processes. Membrane-bound organelles form dynamic contacts with each other to enable the exchange of molecules and to regulate organelle division and positioning in coordination with the cytoskeleton. Crosstalk between the cytoskeleton and dynamic membrane-bound organelles has more recently also been found to regulate cytoskeletal organization. Interestingly, recent work has revealed that, in addition, the cytoskeleton and membrane-bound organelles interact with cytoplasmic biomolecular condensates. The extent and relevance of these complex interactions are just beginning to emerge but may be important for cytoskeletal organization and organelle transport and remodeling. In this review, we highlight these emerging functions and emphasize the complex interplay of the cytoskeleton with these organelles. The crosstalk between membrane-bound organelles, biomolecular condensates and the cytoskeleton in highly polarized cells such as neurons could play essential roles in neuronal development, function and maintenance.
    Keywords cytoskeleton ; organelle contacts ; organelle dynamics ; ER ; neurons ; membraneless organelles ; Biology (General) ; QH301-705.5
    Subject code 612 ; 571
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Stress-induced phase separation of ERES components into Sec bodies precedes ER exit inhibition in mammalian cells.

    van Leeuwen, Wessel / Nguyen, Dan T M / Grond, Rianne / Veenendaal, Tineke / Rabouille, Catherine / Farías, Ginny G

    Journal of cell science

    2022  Volume 135, Issue 23

    Abstract: Phase separation of components of ER exit sites (ERES) into membraneless compartments, the Sec bodies, occurs in Drosophila cells upon exposure to specific cellular stressors, namely, salt stress and amino acid starvation, and their formation is linked ... ...

    Abstract Phase separation of components of ER exit sites (ERES) into membraneless compartments, the Sec bodies, occurs in Drosophila cells upon exposure to specific cellular stressors, namely, salt stress and amino acid starvation, and their formation is linked to the early secretory pathway inhibition. Here, we show Sec bodies also form in secretory mammalian cells upon the same stress. These reversible and membraneless structures are positive for ERES components, including both Sec16A and Sec16B isoforms and COPII subunits. We find that Sec16A, but not Sec16B, is a driver for Sec body formation, and that the coalescence of ERES components into Sec bodies occurs by fusion. Finally, we show that the stress-induced coalescence of ERES components into Sec bodies precedes ER exit inhibition, leading to their progressive depletion from ERES that become non-functional. Stress relief causes an immediate dissolution of Sec bodies and the concomitant restoration of ER exit. We propose that the dynamic conversion between ERES and Sec body assembly, driven by Sec16A, regulates protein exit from the ER during stress and upon stress relief in mammalian cells, thus providing a conserved pro-survival mechanism in response to stress.
    MeSH term(s) Animals ; Endoplasmic Reticulum/metabolism ; COP-Coated Vesicles/metabolism ; Golgi Apparatus/metabolism ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/metabolism ; Secretory Pathway ; Protein Transport ; Mammals/metabolism
    Chemical Substances Vesicular Transport Proteins
    Language English
    Publishing date 2022-12-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.260294
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  9. Article ; Online: Imaging the Polarized Sorting of Proteins from the Golgi Complex in Live Neurons.

    Farías, Ginny G / Britt, Dylan J / Bonifacino, Juan S

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

    2016  Volume 1496, Page(s) 13–30

    Abstract: The study of polarized protein trafficking in live neurons is critical for understanding neuronal structure and function. Given the complex anatomy of neurons and the numerous trafficking pathways that are active in them, however, visualization of ... ...

    Abstract The study of polarized protein trafficking in live neurons is critical for understanding neuronal structure and function. Given the complex anatomy of neurons and the numerous trafficking pathways that are active in them, however, visualization of specific vesicle populations leaving the Golgi complex presents unique challenges. Indeed, several approaches used in non-polarized cells, and even in polarized epithelial cells, have been less successful in neurons. Here, we describe an adaptation of the recently developed Retention Using Selective Hooks (RUSH) system (Boncompain et al., Nat Methods 9:493-498, 2012), previously used in non-polarized cells, to analyze the polarized sorting of proteins from the Golgi complex to dendrites and axons in live neurons. The RUSH system involves the retention of a fluorescently tagged cargo protein fused to the streptavidin-binding peptide (SBP) in the endoplasmic reticulum (ER) through the expression of an ER-hook protein fused to streptavidin. Upon D-biotin addition, the cargo protein is released and its traffic to dendrites and axons can be analyzed in live neurons.
    Language English
    Publishing date 2016
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-6463-5_2
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  10. Article: Mechanisms of Polarized Organelle Distribution in Neurons.

    Britt, Dylan J / Farías, Ginny G / Guardia, Carlos M / Bonifacino, Juan S

    Frontiers in cellular neuroscience

    2016  Volume 10, Page(s) 88

    Abstract: Neurons are highly polarized cells exhibiting axonal and somatodendritic domains with distinct complements of cytoplasmic organelles. Although some organelles are widely distributed throughout the neuronal cytoplasm, others are segregated to either the ... ...

    Abstract Neurons are highly polarized cells exhibiting axonal and somatodendritic domains with distinct complements of cytoplasmic organelles. Although some organelles are widely distributed throughout the neuronal cytoplasm, others are segregated to either the axonal or somatodendritic domains. Recent findings show that organelle segregation is largely established at a pre-axonal exclusion zone (PAEZ) within the axon hillock. Polarized sorting of cytoplasmic organelles at the PAEZ is proposed to depend mainly on their selective association with different microtubule motors and, in turn, with distinct microtubule arrays. Somatodendritic organelles that escape sorting at the PAEZ can be subsequently retrieved at the axon initial segment (AIS) by a microtubule- and/or actin-based mechanism. Dynamic sorting along the PAEZ-AIS continuum can thus explain the polarized distribution of cytoplasmic organelles between the axonal and somatodendritic domains.
    Language English
    Publishing date 2016-03-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2452963-1
    ISSN 1662-5102
    ISSN 1662-5102
    DOI 10.3389/fncel.2016.00088
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