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Rasopathy-Associated Mutation Ptpn11D61Y has Age-Dependent Effect on Synaptic Vesicle Recycling

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F24%3A43921397" target="_blank" >RIV/00023752:_____/24:43921397 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11120/24:43927750

  • Result on the web

    <a href="https://link.springer.com/article/10.1007/s10571-024-01505-1" target="_blank" >https://link.springer.com/article/10.1007/s10571-024-01505-1</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1007/s10571-024-01505-1" target="_blank" >10.1007/s10571-024-01505-1</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Rasopathy-Associated Mutation Ptpn11D61Y has Age-Dependent Effect on Synaptic Vesicle Recycling

  • Original language description

    Rasopathies are genetic disorders often associated with developmental delay and intellectual disability. Noonan syndrome (NS) is one of the most common Rasopathies, caused by mutations in PTPN11 in more than 50% of cases. In mammalian neurons, PTPN11 controls the trafficking of postsynaptic glutamate receptors. This process is disrupted in neurons expressing PTPN11 variants associated with Rasopathies and is thought to contribute to the cognitive impairments in Noonan syndrome. Recent work revealed presynaptic impairments upon expression of RASopathy-linked PTPN11 variants in Drosophila. However, the presynaptic role of PTPN11 has not yet been addressed in mammals. Here, we investigated membrane trafficking of synaptic vesicles in cultured mouse cortical neurons expressing Rasopathy-associated PTPN11D61Y variant. We observed a significantly smaller readily releasable and total recycling pool of synaptic vesicles. The drop in synaptic vesicle release competence was accompanied by a decreased rate of SV retrieval. Interestingly, the presynaptic phenotype was evident in mature (DIV21) but not in immature (DIV12) neurons. Thus, our data reveal importance of balanced PTPN11 activity for normal trafficking of neurotransmitter-filled synaptic vesicles in the presynaptic ending of mature neurons.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30103 - Neurosciences (including psychophysiology)

Result continuities

  • Project

  • Continuities

    V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Others

  • Publication year

    2024

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Cellular and Molecular Neurobiology

  • ISSN

    0272-4340

  • e-ISSN

    1573-6830

  • Volume of the periodical

    44

  • Issue of the periodical within the volume

    1

  • Country of publishing house

    NL - THE KINGDOM OF THE NETHERLANDS

  • Number of pages

    10

  • Pages from-to

    "Article number 77"

  • UT code for WoS article

    001360522800001

  • EID of the result in the Scopus database

    2-s2.0-85209720394