Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants

doi:10.1016/j.yexcr.2005.08.003

Title: Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants

Full Record
Similar

Abstract

The intracellular targeting determinants of oxysterol binding protein (OSBP)-related protein 3 (ORP3) were studied using a series of truncated and point mutated constructs. The pleckstrin homology (PH) domain of ORP3 binds the phosphoinositide-3-kinase (PI3K) products, PI(3,4)P{sub 2} and PI(3,4,5)P{sub 3}. A functional PH domain and flanking sequences are crucial for the plasma membrane (PM) targeting of ORP3. The endoplasmic reticulum (ER) targeting of ORP3 is regulated the by a FFAT motif (EFFDAxE), which mediates interaction with VAMP-associated protein (VAP)-A. The targeting function of the FFAT motif dominates over that of the PH domain. In addition, the exon 10/11 region modulates interaction of ORP3 with the ER and the nuclear membrane. Analysis of a chimeric ORP3:OSBP protein suggests that ligand binding by the C-terminal domain of OSBP induces allosteric changes that activate the N-terminal targeting modules of ORP3. Notably, over-expression of ORP3 together with VAP-A induces stacked ER membrane structures also known as organized smooth ER (OSER). Moreover, lipid starvation promotes formation of dilated peripheral ER (DPER) structures dependent on the ORP3 protein. Based on the present data, we introduce a model for the inter-relationships of the functional domains of ORP3 in the membrane targeting of the protein.

Authors:

Lehto, Markku ^[1]; Hynynen, Riikka ^[1]; Karjalainen, Katja ^[1]; Kuismanen, Esa ^[2]; Hyvaerinen, Kati ^[1]; Olkkonen, Vesa M. ^[3]

Department of Molecular Medicine, National Public Health Institute, Biomedicum, P.O. Box 104, FI-00251 Helsinki (Finland)
Department of Biological and Environmental Sciences, Division of Biochemistry, Viikki Biocenter, P.O. Box 56, Viikinkaari 5, FI-00014 University of Helsinki (Finland)
Department of Molecular Medicine, National Public Health Institute, Biomedicum, P.O. Box 104, FI-00251 Helsinki (Finland). E-mail: vesa.olkkonen@ktl.fi

Publication Date:: Tue Nov 01 00:00:00 EST 2005

OSTI Identifier:: 20717679

Resource Type:: Journal Article

Resource Relation:: Journal Name: Experimental Cell Research; Journal Volume: 310; Journal Issue: 2; Other Information: DOI: 10.1016/j.yexcr.2005.08.003; PII: S0014-4827(05)00378-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; ELECTRON MICROSCOPY; ENDOPLASMIC RETICULUM; LIGANDS; LIPIDS; MEMBRANE PROTEINS; PH VALUE; PHENYLALANINE

Citation Formats


                    Lehto, Markku, Hynynen, Riikka, Karjalainen, Katja, Kuismanen, Esa, Hyvaerinen, Kati, and Olkkonen, Vesa M. Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants.  United States: N. p., 2005. 
        Web.  doi:10.1016/j.yexcr.2005.08.003.

Copy to clipboard


                    Lehto, Markku, Hynynen, Riikka, Karjalainen, Katja, Kuismanen, Esa, Hyvaerinen, Kati, & Olkkonen, Vesa M. Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants.  United States.  doi:10.1016/j.yexcr.2005.08.003.

Copy to clipboard


                    Lehto, Markku, Hynynen, Riikka, Karjalainen, Katja, Kuismanen, Esa, Hyvaerinen, Kati, and Olkkonen, Vesa M. Tue .  
        "Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants".  United States.  
        doi:10.1016/j.yexcr.2005.08.003.

Copy to clipboard


                    
@article{osti_20717679,

  title        = {Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants},

  author       = {Lehto, Markku and Hynynen, Riikka and Karjalainen, Katja and Kuismanen, Esa and Hyvaerinen, Kati and Olkkonen, Vesa M.},

  abstractNote = {The intracellular targeting determinants of oxysterol binding protein (OSBP)-related protein 3 (ORP3) were studied using a series of truncated and point mutated constructs. The pleckstrin homology (PH) domain of ORP3 binds the phosphoinositide-3-kinase (PI3K) products, PI(3,4)P{sub 2} and PI(3,4,5)P{sub 3}. A functional PH domain and flanking sequences are crucial for the plasma membrane (PM) targeting of ORP3. The endoplasmic reticulum (ER) targeting of ORP3 is regulated the by a FFAT motif (EFFDAxE), which mediates interaction with VAMP-associated protein (VAP)-A. The targeting function of the FFAT motif dominates over that of the PH domain. In addition, the exon 10/11 region modulates interaction of ORP3 with the ER and the nuclear membrane. Analysis of a chimeric ORP3:OSBP protein suggests that ligand binding by the C-terminal domain of OSBP induces allosteric changes that activate the N-terminal targeting modules of ORP3. Notably, over-expression of ORP3 together with VAP-A induces stacked ER membrane structures also known as organized smooth ER (OSER). Moreover, lipid starvation promotes formation of dilated peripheral ER (DPER) structures dependent on the ORP3 protein. Based on the present data, we introduce a model for the inter-relationships of the functional domains of ORP3 in the membrane targeting of the protein.},

  doi          = {10.1016/j.yexcr.2005.08.003},

  journal      = {Experimental Cell Research},

  number       = 2,

  volume       = 310,

  place        = {United States},

  year         = {Tue Nov 01 00:00:00 EST 2005},

  month        = {Tue Nov 01 00:00:00 EST 2005}

}

Copy to clipboard

Journal Article:

DOI: 10.1016/j.yexcr.2005.08.003

Other availability

Find in Google Scholar

Search WorldCat to find libraries that may hold this journal

Save / Share:

Export Metadata

Save to My Library

70-kDa peroxisomal membrane protein related protein (P70R/ABCD4) localizes to endoplasmic reticulum not peroxisomes, and NH{sub 2}-terminal hydrophobic property determines the subcellular localization of ABC subfamily D proteins

Kashiwayama, Yoshinori ; Seki, Midori ; Yasui, Akina ; ... - Experimental Cell Research

70-kDa peroxisomal membrane protein related protein (P70R/ABCD4) is a member of ATP-binding cassette (ABC) protein subfamily D. ABC subfamily D proteins are also known as peroxisomal ABC proteins. Therefore, P70R is thought to be a peroxisomal membrane protein. However, the subcellular localization of P70R is not extensively investigated. In this study, we transiently expressed P70R in fusion with HA (P70R-HA) in CHO cells and examined subcellular localization by immunofluorescence. Surprisingly, P70R-HA was localized to the endoplasmic reticulum (ER), not to peroxisomes. To examine the ER-targeting property of P70R, we expressed various NH{sub 2}-terminal deletion constructs of P70R. Among the NH{submore »« less
DOI: 10.1016/j.yexcr.2008.10.031
Glycosylation is essential for translocation of carp retinol-binding protein across the endoplasmic reticulum membrane

Devirgiliis, Chiara ; Gaetani, Sancia ; Apreda, Marianna ; ... - Biochemical and Biophysical Research Communications

Retinoid transport is well characterized in many vertebrates, while it is still largely unexplored in fish. To study the transport and utilization of vitamin A in these organisms, we have isolated from a carp liver cDNA library retinol-binding protein, its plasma carrier. The primary structure of carp retinol-binding protein is very conserved, but presents unique features compared to those of the correspondent proteins isolated and characterized so far in other species: it has an uncleavable signal peptide and two N-glycosylation sites in the NH{sub 2}-terminal region of the protein that are glycosylated in vivo. In this paper, we have investigatedmore »« less
DOI: 10.1016/j.bbrc.2005.04.145
Localization of ras antigenicity in rat hepatocyte plasma membrane and rough endoplasmic reticulum fractions

Dominguez, J.M. ; Lanoix, J. ; Paiement, J. - Experimental Cell Research; (USA)

We have examined the antigenicity of plasma membrane (PM) and rough microsomal (RM) fractions from rat liver using anti-ras monoclonal antibodies 142-24EO5 and Y13-259 and immunochemistry as well as electron microscope immunocytochemistry. Proteins immunoprecipitated with monoclonal antibody 142-24E05 were separated using single-dimensional gradient-gel electrophoresis. The separated proteins were then blotted onto nitrocellulose sheets and incubated with (alpha-32P)GTP. Radioautograms of blots indicated the presence of specific 21.5- and 22-kDa labeled proteins in the PM fraction. A 23.5-kDa (alpha-{sup 32}P) GTP-binding protein was detected in immunoprecipitates of both PM and RM fractions. Monoclonal antibody Y13-259 reacted only with the 21.5-kDa (alpha-{sup 32}P)more »« less
DOI: 10.1016/0014-4827(91)90168-T
A plasma membrane-type Ca[sup 2+]-ATPase of 120 kilodaltons on the endoplasmic reticulum from carrot (Daucus carota) cells

Chen, F.H. ; Ratterman, D.M. ; Sze, H. - Plant Physiology; (United States)

Cytosolic Ca[sup 2+] levels are regulated in part by Ca[sup 2+]-pumping ATPases that export Ca[sup 2+] from the cytoplasm; The types and properties of Ca[sup 2+] pumps in plants are not well understood. The kinetic properties of a 120-kD phosphoenzyme (PE) intermediate formed during the reaction cycle of a Ca[sup 2+]-ATPase from suspension-cultured carrot (Daucus carota) cells are characterized. Only one Ca[sup 2+]-dependent phosphoprotein was formed when carrot membrane vesicles were incubated with [[gamma]-[sup 32]P]ATP. Formation of this 120-kD phosphoprotein was inhibited by vanadate, enhanced by La[sup 3+], and decreased by hydroxylamine, confirming its identification as an intermediate of amore »« less
Discovery of 7-Methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a Potent and Selective First-in-Class Inhibitor of Protein Kinase R (PKR)-like Endoplasmic Reticulum Kinase (PERK)

Axten, Jeffrey M. ; Medina, Jesús R. ; Feng, Yanhong ; ... - Journal of Medicinal Chemistry
DOI: 10.1021/jm300713s