Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family

Abstract The emergence of genes implicated across multiple comorbid neurologic disorders allows to identify shared underlying molecular pathways. Recently, investigation of patients with diverse neurologic disorders found TANC1 and TANC2 as possible candidate disease genes. While the TANC proteins h...

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Autores principales:	Alessandra Gasparini, Silvio C. E. Tosatto, Alessandra Murgia, Emanuela Leonardi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9f4c79e77cbb4bdda097db6a4d6e5c4b
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spelling	oai:doaj.org-article:9f4c79e77cbb4bdda097db6a4d6e5c4b2021-12-02T11:52:35ZDynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family10.1038/s41598-017-05748-52045-2322https://doaj.org/article/9f4c79e77cbb4bdda097db6a4d6e5c4b2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05748-5https://doaj.org/toc/2045-2322Abstract The emergence of genes implicated across multiple comorbid neurologic disorders allows to identify shared underlying molecular pathways. Recently, investigation of patients with diverse neurologic disorders found TANC1 and TANC2 as possible candidate disease genes. While the TANC proteins have been reported as postsynaptic scaffolds influencing synaptic spines and excitatory synapse strength, their molecular functions remain unknown. Here, we conducted a comprehensive in silico analysis of the TANC protein family to characterize their molecular role and understand possible neurobiological consequences of their disruption. The known Ankyrin and tetratricopeptide repeat (TPR) domains have been modeled. The newly predicted N-terminal ATPase domain may function as a regulated molecular switch for downstream signaling. Several putative conserved protein binding motifs allowed to extend the TANC interaction network. Interestingly, we highlighted connections with different signaling pathways converging to modulate neuronal activity. Beyond a known role for TANC family members in the glutamate receptor pathway, they seem linked to planar cell polarity signaling, Hippo pathway, and cilium assembly. This suggests an important role in neuron projection, extension and differentiation.Alessandra GaspariniSilvio C. E. TosattoAlessandra MurgiaEmanuela LeonardiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alessandra Gasparini Silvio C. E. Tosatto Alessandra Murgia Emanuela Leonardi Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family
description	Abstract The emergence of genes implicated across multiple comorbid neurologic disorders allows to identify shared underlying molecular pathways. Recently, investigation of patients with diverse neurologic disorders found TANC1 and TANC2 as possible candidate disease genes. While the TANC proteins have been reported as postsynaptic scaffolds influencing synaptic spines and excitatory synapse strength, their molecular functions remain unknown. Here, we conducted a comprehensive in silico analysis of the TANC protein family to characterize their molecular role and understand possible neurobiological consequences of their disruption. The known Ankyrin and tetratricopeptide repeat (TPR) domains have been modeled. The newly predicted N-terminal ATPase domain may function as a regulated molecular switch for downstream signaling. Several putative conserved protein binding motifs allowed to extend the TANC interaction network. Interestingly, we highlighted connections with different signaling pathways converging to modulate neuronal activity. Beyond a known role for TANC family members in the glutamate receptor pathway, they seem linked to planar cell polarity signaling, Hippo pathway, and cilium assembly. This suggests an important role in neuron projection, extension and differentiation.
format	article
author	Alessandra Gasparini Silvio C. E. Tosatto Alessandra Murgia Emanuela Leonardi
author_facet	Alessandra Gasparini Silvio C. E. Tosatto Alessandra Murgia Emanuela Leonardi
author_sort	Alessandra Gasparini
title	Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family
title_short	Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family
title_full	Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family
title_fullStr	Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family
title_full_unstemmed	Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family
title_sort	dynamic scaffolds for neuronal signaling: in silico analysis of the tanc protein family
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9f4c79e77cbb4bdda097db6a4d6e5c4b
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_version_	1718395000831606784

Dynamic scaffolds for neuronal signaling: in silico analysis of the TANC protein family

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