The VAP protein family: from cellular functions to motor neuron disease

Lev, Sima; Halevy, Daniel Ben; Peretti, Diego; Dahan, Nili

doi:10.1016/j.tcb.2008.03.006

Cited by 206 publications

(228 citation statements)

References 72 publications

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“…Considering that VAP-A and VAP-B are closely related and have redundant functions (Lev et al, 2008), we next examined whether STARD3 and STARD3NL also recruit VAP-B to LE-ER MCS. As expected, VAP-B was recruited to LE-ER MCSs in STARD3-and STARD3NL-expressing cells, and this localization of VAP-B was dependent on its ability to bind FFAT motifs and on the presence of a FFAT motif in STARD3 or STARD3NL (supplementary material Fig.…”

Section: Stard3 and Stard3nl Recruit The Er-resident Vap-a And Vap-b mentioning

confidence: 99%

STARD3/STARD3NL and VAP make a novel molecular tether between late endosomes and the ER

Alpy

Rousseau

Schwab

et al. 2013

Journal of Cell Science

214

254

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SummaryInter-organelle membrane contacts sites (MCSs) are specific subcellular regions favoring the exchange of metabolites and information. We investigated the potential role of the late-endosomal membrane-anchored proteins StAR related lipid transfer domain-3 (STARD3) and STARD3 N-terminal like (STARD3NL) in the formation of MCSs involving late-endosomes (LEs). We demonstrate that both STARD3 and STARD3NL create MCSs between LEs and the endoplasmic reticulum (ER). STARD3 and STARD3NL use a conserved two phenylalanines in an acidic tract (FFAT)-motif to interact with ER-anchored VAP proteins. Together, they form an LE-ER tethering complex allowing heterologous membrane apposition. This LE-ER tethering complex affects organelle dynamics by altering the formation of endosomal tubules. An in situ proximity ligation assay between STARD3, STARD3NL and VAP proteins identified endogenous LE-ER MCS. Thus, we report here the identification of proteins involved in inter-organellar interaction.

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Section: Stard3 and Stard3nl Recruit The Er-resident Vap-a And Vap-b mentioning

confidence: 99%

STARD3/STARD3NL and VAP make a novel molecular tether between late endosomes and the ER

Alpy

Rousseau

Schwab

et al. 2013

Journal of Cell Science

214

254

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“…This family comprises three type II integral ER membrane proteins: VAP-A, VAP-B and VAP-C. 144 They are capable of interacting with the SNAP receptor and FFAT-containing proteins such as OSBP or ceramide transfer protein, thus contributing to membrane fusion and trafficking as well as lipid metabolism. 145 VAPs possess an N-terminal ©2 0 1 1 L a n d e s B i o s c i e n c e .…”

Section: Hcv Assembly and Releasementioning

confidence: 99%

Hepatitis c virus and host cell lipids: An intimate connection

Alvisi¹,

Madan²,

2011

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“…They are composed of an N-terminal immunoglobulin-like ␤ sheet that shares homology with the well-characterized major sperm protein (MSP), a central coiled-coil domain, and a C-terminal transmembrane domain (Lev et al, 2008). VAPs recruit FFAT-motif-containing proteins to the cytosolic surface of the ER membranes, through a conserved region within their MSP domain (Kaiser et al, 2005), and they have been implicated in regulation of membrane transport, phospholipid biosynthesis, and the unfolded protein response.…”

Section: Introductionmentioning

confidence: 99%

Coordinated Lipid Transfer between the Endoplasmic Reticulum and the Golgi Complex Requires the VAP Proteins and Is Essential for Golgi-mediated Transport

Peretti

Dahan

Shimoni

et al. 2008

MBoC

Self Cite

290

272

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Lipid transport between intracellular organelles is mediated by vesicular and nonvesicular transport mechanisms and is critical for maintaining the identities of different cellular membranes. Nonvesicular lipid transport between the endoplasmic reticulum (ER) and the Golgi complex has been proposed to affect the lipid composition of the Golgi membranes. Here, we show that the integral ER-membrane proteins VAP-A and VAP-B affect the structural and functional integrity of the Golgi complex. Depletion of VAPs by RNA interference reduces the levels of phosphatidylinositol-4-phosphate (PI4P), diacylglycerol, and sphingomyelin in the Golgi membranes, and it leads to substantial inhibition of Golgimediated transport events. These effects are coordinately mediated by the lipid-transfer/binding proteins Nir2, oxysterolbinding protein (OSBP), and ceramide-transfer protein (CERT), which interact with VAPs via their FFAT motif. The effect of VAPs on PI4P levels is mediated by the phosphatidylinositol/phosphatidylcholine transfer protein Nir2, which is required for Golgi targeting of OSBP and CERT and the subsequent production of diacylglycerol and sphingomyelin. We propose that Nir2, OSBP, and CERT function coordinately at the ER-Golgi membrane contact sites, thereby affecting the lipid composition of the Golgi membranes and consequently their structural and functional identities. INTRODUCTIONThe unique lipid compositions of the secretory and endocytic organelles are critical for maintaining their distinct structural and functional identities (van Meer, 2000). Their identities are maintained despite extensive interconnecting vesicular-trafficking pathways, and they require tight regulation of lipid sorting, metabolism, and transport (van Meer, 1993;Pomorski et al., 2001;van Meer and Sprong, 2004). Increasing lines of evidence suggest that lipid-transfer proteins (LTPs) play a major role in regulating the lipid composition of membranous organelles (Sprong et al., 2001;De Matteis et al., 2007). These proteins facilitate lipid transfer between a donor and acceptor membrane (Holthuis and Levine, 2005), and they usually contain dual-targeting determinants for different membrane compartments. LTPs have been proposed to efficiently transfer lipids at membrane contact sites (MCSs) (Holthuis and Levine, 2005;Levine and Loewen, 2006).MCSs or zones of close apposition between the ER membranes and other cellular membranes, including the plasma membrane (PM), the membranes of the vacuoles, mitochondria, peroxisomes, lipid droplets, late endosomes, lysosomes, and the Golgi apparatus, have been identified in all eukaryotes by morphological and biochemical studies (Shore and Tata, 1977;Levine, 2004;Levine and Loewen, 2006). More recently, electron tomography studies have identified close contacts (10 -20 nm) between the ER and the outer mitochondrial membrane (Perkins et al., 1997) and between a specialized trans-ER and the three trans-most cisternae of the Golgi complex (Ladinsky et al., 1999;Marsh et al., 2001Marsh et al., , 2004. This ...

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The VAP protein family: from cellular functions to motor neuron disease

Cited by 206 publications

References 72 publications

STARD3/STARD3NL and VAP make a novel molecular tether between late endosomes and the ER

STARD3/STARD3NL and VAP make a novel molecular tether between late endosomes and the ER

Hepatitis c virus and host cell lipids: An intimate connection

Coordinated Lipid Transfer between the Endoplasmic Reticulum and the Golgi Complex Requires the VAP Proteins and Is Essential for Golgi-mediated Transport

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