echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Biochemistry News > Biotechnology News > Groundbreaking new research: Organelle contact regulation

    Groundbreaking new research: Organelle contact regulation

    • Last Update: 2022-01-23
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com


    Phosphorylation of the ACBD5 FFAT domain regulates the interaction with VAPB and thus the peroxisome-ER interaction, which is different

    Source: University of Exeter

    New discovery of organelle contact regulation

    A groundbreaking study has revealed how cellular compartments (organelles) control how they interact and cooperate


    The research, led by Professor Michael Schrader and Dr Joseph Costello from the University of Exeter, builds on their recent discovery of two organelles - known as the peroxisome and the endoplasmic reticulum (ER).


    This cooperation is critical for the production of specific lipids that are critical to nerve cell function and protect cells from oxidative damage


    Organelles are the functional units of cells


    For cells and organisms to survive, organelles must interact and cooperate


    How this is mediated and regulated in cells is an important and challenging question in cell biology


    In a previous study, the researchers found that a protein in the peroxisome called ACBD5 directly interacts with a protein in the endoplasmic reticulum called VAPB


    This interaction links the two organelles together and allows lipid transfer between them


    The new study sheds light on how this interaction is regulated at the molecular level


    "Organelles don't always connect with each other, which would be disadvantageous," Professor Schreeder said


    "They also need to keep their distance and change their position in the cell to encounter other organelles


    Therefore, membrane contacts between organelles need to be dynamic


    "Our findings reveal how the regulation of peroxisome-ER contacts works in mammalian cells and provide the first clear example of the physiological role of peroxisomal protein phosphorylation," Dr.


    Phosphorylation reactions are key to many cellular processes in biology


    The addition (or removal) of phosphate to a protein can alter its properties, thereby altering its function or activity


    Therefore, protein phosphorylation/dephosphorylation is an important regulatory mechanism in cells
    .

    It is done by enzymes such as kinases, which mediate protein phosphorylation, and phosphatases, which remove phosphorylation (dephosphorylation)
    .

    The researchers found that a binding motif of ACBD5, called the FFAT motif, is required for interaction with the VAPB protein domain, and it can be phosphorylated at multiple amino acids
    .

    Notably, phosphorylation of only one amino acid in the core region of the FFAT motif prevents ACBD5 from binding to VAPB and inhibits peroxisome-ER membrane contact
    .

    In addition, the researchers discovered an enzyme, a kinase called GSK3β, that phosphorylates ACBD5 in cells
    .

    In addition, we identified other phosphorylation sites near the core region, and phosphorylation at these sites facilitated the ACBD5-VAPB interaction, revealing a complex regulatory mechanism
    .

    The researchers collaborated with the laboratory of Professor Bettina Warscheid at the University of Freiburg in Germany, an expert in phosphoproteomics
    .

    "The FFAT motif is found in many other proteins that are involved in VAP protein interactions elsewhere in the cell," Professor Schrader said
    .

    "Our findings extend current FFAT patterns and point to a general mechanism by which they are regulated by phosphorylation
    .

    "Understanding how they are regulated is also relevant to disease
    .
    "

    ACBD5-deficient patients suffer from peroxisomal disease that severely damages the brain and retina, affecting vision, while VAPB and GSK3β have been linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)
    .

    People with severe peroxisomal disease, also known as Zellweger spectrum disorder, often die in childhood or youth, the team collaborated with researchers from the Amsterdam Academic Medical Centre and a charity called Zellweger UK Agency experts collaborate to address peroxisomal disorders, raise awareness, and support families and patients
    .

    article title

    Regulating peroxisome-ER contacts via the ACBD5-VAPB tether by FFAT motif phosphorylation and GSK3β

    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.