GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation

Glutamate transporter associated protein 3–18 (GTRAP3-18) is an endoplasmic reticulum (ER)-localized protein belonging to the prenylated rab-acceptor-family interacting with small Rab GTPases, which regulate intracellular trafficking events. Its impact on secretory trafficking has not been investiga...

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Main Authors:	Maier, S, Reiterer, V, Ruggiero, A M, Rothstein, J D, Thomas, S, Dahm, R, Sitte, H H, Farhan, H
Format:	Online
Language:	English
Published:	Blackwell Publishing Ltd 2009
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823040/

id	pubmed-3823040
recordtype	oai_dc
spelling	pubmed-38230402015-04-27 GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation Maier, S Reiterer, V Ruggiero, A M Rothstein, J D Thomas, S Dahm, R Sitte, H H Farhan, H Articles Glutamate transporter associated protein 3–18 (GTRAP3-18) is an endoplasmic reticulum (ER)-localized protein belonging to the prenylated rab-acceptor-family interacting with small Rab GTPases, which regulate intracellular trafficking events. Its impact on secretory trafficking has not been investigated. We report here that GTRAP3-18 has an inhibitory effect on Rab1, which is involved in ER-to-Golg trafficking. The effects on the early secretory pathway in HEK293 cells were: reduction of the rate of ER-to-Golgi transport of the vesicular stomatitis virus glycoprotein (VSVG), slowed accumulation of a Golgi marker plasmid in pre-Golgi structures after Brefeldin A treatment and inhibition of cargo concentration of the neuronal glutamate transporter excitatory amino-acid carrier 1 (EAAC1) into transpor complexes in HEK293 cells, an effect that could be completely reversed in the presence of an excess of Rab1. In accordance with the known role of Rab1 in neurite formation, overexpression of GTRAP3-18 significantly inhibited the length of outgrowing neurites in differentiated CAD cells. The inhibitory effect of GTRAP3-18 on neurite growth was rescued by co-expression with Rab1, supporting the conclusion that GTRAP 3-18 acted by inhibiting Rab1 action. Finally, we hypothesized that expression of GTRAP3-18 in the brain shoul be lower at stages of active synaptogenesis compared to early developmental stages. This was the case as expression of GTRAP3-18 declined from E17 to P0 and adult rat brains. Thus, we propose a model where protein trafficking and neuronal differentiation are directly linked by the interaction of Rab1 and its regulator GTRAP3-18. Blackwell Publishing Ltd 2009-01 2008-03-17 /pmc/articles/PMC3823040/ /pubmed/18363836 http://dx.doi.org/10.1111/j.1582-4934.2008.00303.x Text en © 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Maier, S Reiterer, V Ruggiero, A M Rothstein, J D Thomas, S Dahm, R Sitte, H H Farhan, H
spellingShingle	Maier, S Reiterer, V Ruggiero, A M Rothstein, J D Thomas, S Dahm, R Sitte, H H Farhan, H GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation
author_facet	Maier, S Reiterer, V Ruggiero, A M Rothstein, J D Thomas, S Dahm, R Sitte, H H Farhan, H
author_sort	Maier, S
title	GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation
title_short	GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation
title_full	GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation
title_fullStr	GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation
title_full_unstemmed	GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation
title_sort	gtrap3-18 serves as a negative regulator of rab1 in protein transport and neuronal differentiation
description	Glutamate transporter associated protein 3–18 (GTRAP3-18) is an endoplasmic reticulum (ER)-localized protein belonging to the prenylated rab-acceptor-family interacting with small Rab GTPases, which regulate intracellular trafficking events. Its impact on secretory trafficking has not been investigated. We report here that GTRAP3-18 has an inhibitory effect on Rab1, which is involved in ER-to-Golg trafficking. The effects on the early secretory pathway in HEK293 cells were: reduction of the rate of ER-to-Golgi transport of the vesicular stomatitis virus glycoprotein (VSVG), slowed accumulation of a Golgi marker plasmid in pre-Golgi structures after Brefeldin A treatment and inhibition of cargo concentration of the neuronal glutamate transporter excitatory amino-acid carrier 1 (EAAC1) into transpor complexes in HEK293 cells, an effect that could be completely reversed in the presence of an excess of Rab1. In accordance with the known role of Rab1 in neurite formation, overexpression of GTRAP3-18 significantly inhibited the length of outgrowing neurites in differentiated CAD cells. The inhibitory effect of GTRAP3-18 on neurite growth was rescued by co-expression with Rab1, supporting the conclusion that GTRAP 3-18 acted by inhibiting Rab1 action. Finally, we hypothesized that expression of GTRAP3-18 in the brain shoul be lower at stages of active synaptogenesis compared to early developmental stages. This was the case as expression of GTRAP3-18 declined from E17 to P0 and adult rat brains. Thus, we propose a model where protein trafficking and neuronal differentiation are directly linked by the interaction of Rab1 and its regulator GTRAP3-18.
publisher	Blackwell Publishing Ltd
publishDate	2009
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823040/
_version_	1612025208894390272

GTRAP3-18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation

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