دورية أكاديمية
Drebrin Regulates Acetylcholine Receptor Clustering and Organization of Microtubules at the Postsynaptic Machinery
العنوان: | Drebrin Regulates Acetylcholine Receptor Clustering and Organization of Microtubules at the Postsynaptic Machinery |
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المؤلفون: | Paloma Alvarez-Suarez, Natalia Nowak, Anna Protasiuk-Filipunas, Hiroyuki Yamazaki, Tomasz J. Prószyński, Marta Gawor |
المصدر: | International Journal of Molecular Sciences, Vol 22, Iss 17, p 9387 (2021) |
بيانات النشر: | MDPI AG, 2021. |
سنة النشر: | 2021 |
المجموعة: | LCC:Biology (General) LCC:Chemistry |
مصطلحات موضوعية: | drebrin, EB3, rapsyn, AChR clustering, actin, microtubules, Biology (General), QH301-705.5, Chemistry, QD1-999 |
الوصف: | Proper muscle function depends on the neuromuscular junctions (NMJs), which mature postnatally to complex “pretzel-like” structures, allowing for effective synaptic transmission. Postsynaptic acetylcholine receptors (AChRs) at NMJs are anchored in the actin cytoskeleton and clustered by the scaffold protein rapsyn, recruiting various actin-organizing proteins. Mechanisms driving the maturation of the postsynaptic machinery and regulating rapsyn interactions with the cytoskeleton are still poorly understood. Drebrin is an actin and microtubule cross-linker essential for the functioning of the synapses in the brain, but its role at NMJs remains elusive. We used immunohistochemistry, RNA interference, drebrin inhibitor 3,5-bis-trifluoromethyl pyrazole (BTP2) and co-immunopreciptation to explore the role of this protein at the postsynaptic machinery. We identify drebrin as a postsynaptic protein colocalizing with the AChRs both in vitro and in vivo. We also show that drebrin is enriched at synaptic podosomes. Downregulation of drebrin or blocking its interaction with actin in cultured myotubes impairs the organization of AChR clusters and the cluster-associated microtubule network. Finally, we demonstrate that drebrin interacts with rapsyn and a drebrin interactor, plus-end-tracking protein EB3. Our results reveal an interplay between drebrin and cluster-stabilizing machinery involving rapsyn, actin cytoskeleton, and microtubules. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1422-0067 1661-6596 |
Relation: | https://www.mdpi.com/1422-0067/22/17/9387; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
DOI: | 10.3390/ijms22179387 |
URL الوصول: | https://doaj.org/article/2177491f14a540cb9f3901d9d72649c1 |
رقم الأكسشن: | edsdoj.2177491f14a540cb9f3901d9d72649c1 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14220067 16616596 |
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DOI: | 10.3390/ijms22179387 |