Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling

Abstract GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs) play essential roles in regulating the activity of small GTPases. Several GAPs and GEFs have been shown to be present at the postsynaptic density (PSD) within excitatory glutamatergic neurons and regulate the activity of...

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Autores principales:	Brent Wilkinson, Jing Li, Marcelo P. Coba
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fb039a57560646a886a69c1f53f3cebd
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spelling	oai:doaj.org-article:fb039a57560646a886a69c1f53f3cebd2021-12-02T12:32:06ZSynaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling10.1038/s41598-017-05588-32045-2322https://doaj.org/article/fb039a57560646a886a69c1f53f3cebd2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05588-3https://doaj.org/toc/2045-2322Abstract GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs) play essential roles in regulating the activity of small GTPases. Several GAPs and GEFs have been shown to be present at the postsynaptic density (PSD) within excitatory glutamatergic neurons and regulate the activity of glutamate receptors. However, it is not known how synaptic GAP and GEF proteins are organized within the PSD signaling machinery, if they have overlapping interaction networks, or if they associate with proteins implicated in contributing to psychiatric disease. Here, we determine the interactomes of three interacting GAP/GEF proteins at the PSD, including the RasGAP Syngap1, the ArfGAP Agap2, and the RhoGEF Kalirin, which includes a total of 280 interactions. We describe the functional properties of each interactome and show that these GAP/GEF proteins are highly associated with and cluster other proteins directly involved in GTPase signaling mechanisms. We also utilize Agap2 as an example of GAP/GEFs localized within multiple neuronal compartments and determine an additional 110 interactions involving Agap2 outside of the PSD. Functional analysis of PSD and non-PSD interactomes illustrates both common and unique functions of Agap2 determined by its subcellular location. Furthermore, we also show that these GAPs/GEFs associate with several proteins involved in psychiatric disease.Brent WilkinsonJing LiMarcelo P. CobaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brent Wilkinson Jing Li Marcelo P. Coba Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling
description	Abstract GTPase-activating proteins (GAPs) and guanine exchange factors (GEFs) play essential roles in regulating the activity of small GTPases. Several GAPs and GEFs have been shown to be present at the postsynaptic density (PSD) within excitatory glutamatergic neurons and regulate the activity of glutamate receptors. However, it is not known how synaptic GAP and GEF proteins are organized within the PSD signaling machinery, if they have overlapping interaction networks, or if they associate with proteins implicated in contributing to psychiatric disease. Here, we determine the interactomes of three interacting GAP/GEF proteins at the PSD, including the RasGAP Syngap1, the ArfGAP Agap2, and the RhoGEF Kalirin, which includes a total of 280 interactions. We describe the functional properties of each interactome and show that these GAP/GEF proteins are highly associated with and cluster other proteins directly involved in GTPase signaling mechanisms. We also utilize Agap2 as an example of GAP/GEFs localized within multiple neuronal compartments and determine an additional 110 interactions involving Agap2 outside of the PSD. Functional analysis of PSD and non-PSD interactomes illustrates both common and unique functions of Agap2 determined by its subcellular location. Furthermore, we also show that these GAPs/GEFs associate with several proteins involved in psychiatric disease.
format	article
author	Brent Wilkinson Jing Li Marcelo P. Coba
author_facet	Brent Wilkinson Jing Li Marcelo P. Coba
author_sort	Brent Wilkinson
title	Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling
title_short	Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling
title_full	Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling
title_fullStr	Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling
title_full_unstemmed	Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling
title_sort	synaptic gap and gef complexes cluster proteins essential for gtp signaling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fb039a57560646a886a69c1f53f3cebd
work_keys_str_mv	AT brentwilkinson synapticgapandgefcomplexesclusterproteinsessentialforgtpsignaling AT jingli synapticgapandgefcomplexesclusterproteinsessentialforgtpsignaling AT marcelopcoba synapticgapandgefcomplexesclusterproteinsessentialforgtpsignaling
_version_	1718394194931744768

Synaptic GAP and GEF Complexes Cluster Proteins Essential for GTP Signaling

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