Article

The PX-BAR membrane-remodeling unit of sorting nexin 9.

Department of Physical Biochemistry, Max-Planck-Institute for Molecular Physiology, Dortmund, Germany.
The EMBO Journal (Impact Factor: 10.75). 12/2007; 26(22):4788-800. DOI: 10.1038/sj.emboj.7601889
Source: PubMed

ABSTRACT Sorting nexins (SNXs) form a family of proteins known to interact with components in the endosomal system and to regulate various steps of vesicle transport. Sorting nexin 9 (SNX9) is involved in the late stages of clathrin-mediated endocytosis in non-neuronal cells, where together with the GTPase dynamin, it participates in the formation and scission of the vesicle neck. We report here crystal structures of the functional membrane-remodeling unit of SNX9 and show that it efficiently tubulates lipid membranes in vivo and in vitro. Elucidation of the protein superdomain structure, together with mutational analysis and biochemical and cell biological experiments, demonstrated how the SNX9 PX and BAR domains work in concert in targeting and tubulation of phosphoinositide-containing membranes. The study provides insights into the SNX9-induced membrane modulation mechanism.

0 Followers
 · 
72 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Caveolae are invaginations of the cell surface thought to regulate membrane tension, signalling, adhesion and lipid homeostasis due to their dynamic behaviour ranging from stable surface association to dynamic rounds of fission and fusion with the plasma membrane. The caveolae coat is generated by oligomerisation of the membrane protein caveolin and the family of cavin proteins. Here, we show that cavin3 is targeted to caveolae by cavin1 where it interacts with the scaffolding domain of caveolin1 and promote caveolae dynamics. We found that the N-terminal region of cavin3 binds a trimer of the cavin1 N-terminus in competition with a homologous cavin2 region, showing that the cavins form distinct subcomplexes via their N-terminal regions. Our data shows that cavin3 is enriched at deeply invaginated caveolae and that loss of cavin3 in cells results in an increase of stable caveolae and a decrease of caveolae with short duration time at the membrane. We propose that cavin3 is recruited to the caveolae coat by cavin1 to interact with caveolin1 and regulate the duration time of caveolae at the plasma membrane.
    Journal of Cell Science 01/2015; 128(5). DOI:10.1242/jcs.161463 · 5.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phosphatidylinositol 4,5-bisphosphate (PI4,5P2) is an essential lipid messenger with roles in all eukaryotes and most aspects of human physiology. By controlling the targeting and activity of its effectors, PI4,5P2 modulates processes, such as cell migration, vesicular trafficking, cellular morphogenesis, signaling and gene expression. In cells, PI4,5P2 has a much higher concentration than other phosphoinositide species and its total content is largely unchanged in response to extracellular stimuli. The discovery of a vast array of PI4,5P2 binding proteins is consistent with data showing that the majority of cellular PI4,5P2 is sequestered. This supports a mechanism where PI4,5P2 functions as a localized and highly specific messenger. Further support of this mechanism comes from the de novo synthesis of PI4,5P2 which is often linked with PIP kinase interaction with PI4,5P2 effectors and is a mechanism to define specificity of PI4,5P2 signaling. The association of PI4,5P2-generating enzymes with PI4,5P2 effectors regulate effector function both temporally and spatially in cells. In this review, the PI4,5P2 effectors whose functions are tightly regulated by associations with PI4,5P2-generating enzymes will be discussed. This article is part of a Special Issue entitled Phosphoinositides.
    Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 01/2015; 1851(6). DOI:10.1016/j.bbalip.2015.01.009 · 4.50 Impact Factor
  • Source

Full-text (2 Sources)

Download
8 Downloads
Available from
Aug 21, 2014