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

Pęziński, Marcin; Maliszewska-Olejniczak, Kamila; Daszczuk, Patrycja; Mazurek, Paula; Niewiadomski, Paweł; Rędowicz, Maria Jolanta

doi:10.3390/ijms222112051

Open AccessArticle

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

by

Marcin Pęziński

^1,2,*,

Kamila Maliszewska-Olejniczak

^1,†,

Patrycja Daszczuk

¹,

Paula Mazurek

¹,

Paweł Niewiadomski

^1,3

and

Maria Jolanta Rędowicz

²

¹

Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-787 Warszawa, Poland

²

Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-787 Warszawa, Poland

³

Centre of New Technologies, Laboratory of Molecular and Cellular Signalling, University of Warsaw, 2c Stefan Banach St., 02-787 Warszawa, Poland

^*

Author to whom correspondence should be addressed.

^†

Current address: Warsaw University of Life Sciences, 166 Nowoursynowska St., 02-787 Warszawa, Poland.

Int. J. Mol. Sci. 2021, 22(21), 12051; https://doi.org/10.3390/ijms222112051

Submission received: 8 October 2021 / Revised: 3 November 2021 / Accepted: 4 November 2021 / Published: 7 November 2021

(This article belongs to the Special Issue Molecular Research on Muscle Protein and Myopathies 2.0)

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Abstract

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.

Keywords: actin; neuromuscular junction; podosomes; postsynaptic machinery; rapsyn; Tks5

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MDPI and ACS Style

Pęziński, M.; Maliszewska-Olejniczak, K.; Daszczuk, P.; Mazurek, P.; Niewiadomski, P.; Rędowicz, M.J. Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction. Int. J. Mol. Sci. 2021, 22, 12051. https://doi.org/10.3390/ijms222112051

AMA Style

Pęziński M, Maliszewska-Olejniczak K, Daszczuk P, Mazurek P, Niewiadomski P, Rędowicz MJ. Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction. International Journal of Molecular Sciences. 2021; 22(21):12051. https://doi.org/10.3390/ijms222112051

Chicago/Turabian Style

Pęziński, Marcin, Kamila Maliszewska-Olejniczak, Patrycja Daszczuk, Paula Mazurek, Paweł Niewiadomski, and Maria Jolanta Rędowicz. 2021. "Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction" International Journal of Molecular Sciences 22, no. 21: 12051. https://doi.org/10.3390/ijms222112051

APA Style

Pęziński, M., Maliszewska-Olejniczak, K., Daszczuk, P., Mazurek, P., Niewiadomski, P., & Rędowicz, M. J. (2021). Tks5 Regulates Synaptic Podosome Formation and Stabilization of the Postsynaptic Machinery at the Neuromuscular Junction. International Journal of Molecular Sciences, 22(21), 12051. https://doi.org/10.3390/ijms222112051

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

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