A journey through the exocytic pathway

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Crystal structure of Sar1-GDP at 1.7 Å resolution and the role of the NH2 terminus in ER export

The Sar1 GTPase is an essential component of COPII vesicle coats involved in export of cargo from the ER. We report the 1.7-Å structure of Sar1 and find that consistent with the sequence divergence of Sar1 from Arf family GTPases, Sar1 is structurally distinct. In particular, we show that the Sar1 NH2 terminus contains two regions: an NH2-terminal extension containing an evolutionary conserved hydrophobic motif that facilitates membrane recruitment and activation by the mammalian Sec12 guanine nucleotide exchange factor, and an α1' amphipathic helix that contributes to interaction with the Sec23/24 complex that is responsible for cargo selection during ER export. We propose that the hydrophobic Sar1 NH2-terminal activation/recruitment motif, in conjunction with the α1' helix, mediates the initial steps in COPII coat assembly for export from the ER

Spadin, a Sortilin-Derived Peptide, Targeting Rodent TREK-1 Channels: A New Concept in the Antidepressant Drug Design

We found that spadin, a natural peptide derived from sortilin, blocks the mouse TREK-1 channel and might be an efficient and fast-acting antidepressant

Focal Adhesion Kinase-Dependent Role of the Soluble Form of Neurotensin Receptor-3/Sortilin in Colorectal Cancer Cell Dissociation

The aim of the present review is to unravel the mechanisms of action of the soluble form of the neurotensin (NT) receptor-3 (NTSR3), also called Sortilin, in numerous physiopathological processes including cancer development, cardiovascular diseases and depression. Sortilin/NTSR3 is a transmembrane protein thought to exert multiple functions both intracellularly and at the level of the plasma membrane. The Sortilin/NTSR3 extracellular domain is released by shedding from all the cells expressing the protein. Although the existence of the soluble form of Sortilin/NTSR3 (sSortilin/NTSR3) has been evidenced for more than 10 years, the studies focusing on the role of this soluble protein at the mechanistic level remain rare. Numerous cancer cells, including colonic cancer cells, express the receptor family of neurotensin (NT), and particularly Sortilin/NTSR3. This review aims to summarize the functional role of sSortilin/NTSR3 characterized in the colonic cancer cell line HT29. This includes mechanisms involving signaling cascades through focal adhesion kinase (FAK), a key pathway leading to the weakening of cell–cell and cell–extracellular matrix adhesions, a series of events which could be responsible for cancer metastasis. Finally, some future approaches targeting the release of sNTSR3 through the inhibition of matrix metalloproteases (MMPs) are suggested

[28] Expression, purification, and measurements of activity of ARNO1, a guanine nucleotide exchange factor for ADP-ribosylation factor 1 (ARF1)

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N-Terminal Hydrophobic Residues of the G-Protein ADP-Ribosylation Factor-1 Insert into Membrane Phospholipids upon GDP to GTP Exchange †

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Dual Interaction of ADP Ribosylation Factor 1 with Sec7 Domain and with Lipid Membranes during Catalysis of Guanine Nucleotide Exchange

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Bridging the Gap Between Diabetes and Stroke in Search of High Clinical Relevance Therapeutic Targets

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The Anti-Apoptotic Role of Neurotensin

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Neurotensin receptor-2 and -3 are crucial for the anti-apoptotic effect of neurotensin on pancreatic β-TC3 cells

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