Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction

Currently, the etiology of many neuromuscular disorders remains unknown. Many of them are characterized by aberrations in the maturation of the neuromuscular junction (NMJ) postsynaptic machinery. Unfortunately, the molecular factors involved in this process are still largely unknown, which poses a...

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Autores principales:	Marcin Pęziński, Kamila Maliszewska-Olejniczak, Patrycja Daszczuk, Paula Mazurek, Paweł Niewiadomski, Maria Jolanta Rędowicz
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	actin neuromuscular junction podosomes postsynaptic machinery rapsyn Tks5 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/16b3d7fa41e94544b14c0ef10c9e4075
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spelling	oai:doaj.org-article:16b3d7fa41e94544b14c0ef10c9e40752021-11-11T17:26:49ZTks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction10.3390/ijms2221120511422-00671661-6596https://doaj.org/article/16b3d7fa41e94544b14c0ef10c9e40752021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12051https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Currently, the etiology of many neuromuscular disorders remains unknown. Many of them are characterized by aberrations in the maturation of the neuromuscular junction (NMJ) postsynaptic machinery. Unfortunately, the molecular factors involved in this process are still largely unknown, which poses a great challenge for identifying potential therapeutic targets. Here, we identified Tks5 as a novel interactor of αdystrobrevin-1, which is a crucial component of the NMJ postsynaptic machinery. Tks5 has been previously shown in cancer cells to be an important regulator of actin-rich structures known as invadosomes. However, a role of this scaffold protein at a synapse has never been studied. We show that Tks5 is crucial for remodeling of the NMJ postsynaptic machinery by regulating the organization of structures similar to the invadosomes, known as synaptic podosomes. Additionally, it is involved in the maintenance of the integrity of acetylcholine receptor (AChR) clusters and regulation of their turnover. Lastly, our data indicate that these Tks5 functions may be mediated by its involvement in recruitment of actin filaments to the postsynaptic machinery. Collectively, we show for the first time that the Tks5 protein is involved in regulation of the postsynaptic machinery.Marcin PęzińskiKamila Maliszewska-OlejniczakPatrycja DaszczukPaula MazurekPaweł NiewiadomskiMaria Jolanta RędowiczMDPI AGarticleactinneuromuscular junctionpodosomespostsynaptic machineryrapsynTks5Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12051, p 12051 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	actin neuromuscular junction podosomes postsynaptic machinery rapsyn Tks5 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	actin neuromuscular junction podosomes postsynaptic machinery rapsyn Tks5 Biology (General) QH301-705.5 Chemistry QD1-999 Marcin Pęziński Kamila Maliszewska-Olejniczak Patrycja Daszczuk Paula Mazurek Paweł Niewiadomski Maria Jolanta Rędowicz Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction
description	Currently, the etiology of many neuromuscular disorders remains unknown. Many of them are characterized by aberrations in the maturation of the neuromuscular junction (NMJ) postsynaptic machinery. Unfortunately, the molecular factors involved in this process are still largely unknown, which poses a great challenge for identifying potential therapeutic targets. Here, we identified Tks5 as a novel interactor of αdystrobrevin-1, which is a crucial component of the NMJ postsynaptic machinery. Tks5 has been previously shown in cancer cells to be an important regulator of actin-rich structures known as invadosomes. However, a role of this scaffold protein at a synapse has never been studied. We show that Tks5 is crucial for remodeling of the NMJ postsynaptic machinery by regulating the organization of structures similar to the invadosomes, known as synaptic podosomes. Additionally, it is involved in the maintenance of the integrity of acetylcholine receptor (AChR) clusters and regulation of their turnover. Lastly, our data indicate that these Tks5 functions may be mediated by its involvement in recruitment of actin filaments to the postsynaptic machinery. Collectively, we show for the first time that the Tks5 protein is involved in regulation of the postsynaptic machinery.
format	article
author	Marcin Pęziński Kamila Maliszewska-Olejniczak Patrycja Daszczuk Paula Mazurek Paweł Niewiadomski Maria Jolanta Rędowicz
author_facet	Marcin Pęziński Kamila Maliszewska-Olejniczak Patrycja Daszczuk Paula Mazurek Paweł Niewiadomski Maria Jolanta Rędowicz
author_sort	Marcin Pęziński
title	Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction
title_short	Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction
title_full	Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction
title_fullStr	Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction
title_full_unstemmed	Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction
title_sort	tks5 regulates synaptic podosome formation and stabilization of the postsynaptic machinery at the neuromuscular junction
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/16b3d7fa41e94544b14c0ef10c9e4075
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_version_	1718432046321238016

Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction

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