Rasopathy-Associated Mutation Ptpn11D61Y has Age-Dependent Effect on Synaptic Vesicle Recycling
Jazyk angličtina Země Nizozemsko Médium electronic
Typ dokumentu časopisecké články
Grantová podpora
01GM1902B
Bundesministerium für Bildung und Forschung
01GM1902B
Bundesministerium für Bildung und Forschung
101080580
European Commission
101080580
European Commission
PubMed
39570442
PubMed Central
PMC11582327
DOI
10.1007/s10571-024-01505-1
PII: 10.1007/s10571-024-01505-1
Knihovny.cz E-zdroje
- MeSH
- kultivované buňky MeSH
- mutace genetika MeSH
- myši MeSH
- neurony metabolismus MeSH
- stárnutí genetika metabolismus MeSH
- synaptické vezikuly * metabolismus MeSH
- tyrosinfosfatasa nereceptorového typu 11 * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- Ptpn11 protein, mouse MeSH Prohlížeč
- tyrosinfosfatasa nereceptorového typu 11 * MeSH
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.
3rd Faculty of Medicine Charles University Prague Czech Republic
National Institute of Mental Health Klecany Czech Republic
RG Presynaptic Plasticity Leibniz Institute for Neurobiology Magdeburg Germany
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