Role of LBPA and Alix in Multivesicular Liposome Formation and Endosome Organization

What are the components that control the assembly of subcellular organelles in eukaryotic cells? Although membranes can clearly be distorted by cytosolic factors, very little is known about the intrinsic mechanisms that control the biogenesis, shape, and organization of organellar membranes. Here, we found that the unconventional phospholipid lysobisphosphatidic acid (LBPA) could induce the formation of multivesicular liposomes that resembled the multivesicular endosomes that exist where this lipid is found in vivo. This process depended on the same pH gradient that exists across endosome membranes in vivo and was selectively controlled by Alix. In turn, Alix regulated the organization of LBPA-containing endosomes in vivo.

[1]  S. Emr,et al.  Receptor downregulation and multivesicular-body sorting , 2002, Nature Reviews Molecular Cell Biology.

[2]  I. Mellman,et al.  Cytoplasmic coat proteins involved in endosome function , 1995, Cell.

[3]  M. Lindsay,et al.  Interaction of anti-phospholipid antibodies with late endosomes of human endothelial cells. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[4]  S. Emr,et al.  Bro1 is an endosome-associated protein that functions in the MVB pathway in Saccharomyces cerevisiae , 2003, Journal of Cell Science.

[5]  B. Blot,et al.  Alix (ALG-2-interacting Protein X), a Protein Involved in Apoptosis, Binds to Endophilins and Induces Cytoplasmic Vacuolization* , 2002, The Journal of Biological Chemistry.

[6]  H. Goodson,et al.  Late endosome motility depends on lipids via the small GTPase Rab7 , 2002, The EMBO journal.

[7]  W. Sundquist,et al.  The Protein Network of HIV Budding , 2003, Cell.

[8]  A. Calistri,et al.  AIP1/ALIX Is a Binding Partner for HIV-1 p6 and EIAV p9 Functioning in Virus Budding , 2003, Cell.

[9]  H. Geuze,et al.  Selective Enrichment of Tetraspan Proteins on the Internal Vesicles of Multivesicular Endosomes and on Exosomes Secreted by Human B-lymphocytes* , 1998, The Journal of Biological Chemistry.

[10]  S. Matile,et al.  Spectroscopic detection of endovesiculation by large unilamellar phosphatidylcholine vesicles: effects of chlorpromazine, dibucaine, and safingol. , 1999, Bioorganic & medicinal chemistry.

[11]  Etienne Gagnon,et al.  The Phagosome Proteome: Insight into Phagosome Functions , 2001 .

[12]  R. Palmiter,et al.  Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport , 1999, Nature Cell Biology.

[13]  J. Dubochet,et al.  Cryo-electron microscopy of vitrified specimens , 1988, Quarterly Reviews of Biophysics.

[14]  J. Gruenberg,et al.  Sonic Hedgehog Induces the Segregation of Patched and Smoothened in Endosomes , 2002, Current Biology.

[15]  J. Dubochet,et al.  The cell in absence of aggregation artifacts. , 2001, Micron.

[16]  R. Parton,et al.  Annexin II regulates multivesicular endosome biogenesis in the degradation pathway of animal cells , 2003, The EMBO journal.

[17]  I. Mellman,et al.  Inhibition of Endosome Function in CHO Cells Bearing a Temperature-sensitive Defect in the Coatomer (COPI) Component ε-COP , 1997, The Journal of cell biology.

[18]  P. Ricciardi-Castagnoli,et al.  Proteomic Analysis of Dendritic Cell-Derived Exosomes: A Secreted Subcellular Compartment Distinct from Apoptotic Vesicles1 , 2001, The Journal of Immunology.

[19]  C. Machamer,et al.  The envelope of vaccinia virus reveals an unusual phospholipid in Golgi complex membranes. , 1996, Journal of cell science.

[20]  R. Parton,et al.  A lipid associated with the antiphospholipid syndrome regulates endosome structure and function , 1998, Nature.

[21]  E. Kuismanen,et al.  Heterogeneous distribution of the unusual phospholipid semilysobisphosphatidic acid through the Golgi complex. , 1997, Molecular biology of the cell.

[22]  S. Matile,et al.  Rapid access to synthetic lysobisphosphatidic acids using P(III) chemistry. , 2000, Organic letters.

[23]  Jean Gruenberg,et al.  The endocytic pathway: a mosaic of domains , 2001, Nature Reviews Molecular Cell Biology.

[24]  A. Rudensky,et al.  Reorganization of multivesicular bodies regulates MHC class II antigen presentation by dendritic cells , 2001, The Journal of cell biology.

[25]  A. Nichols,et al.  Alix, a novel mouse protein undergoing calcium-dependent interaction with the apoptosis-linked-gene 2 (ALG-2) protein , 1999, Cell Death and Differentiation.

[26]  P. Cosson,et al.  Separation and Characterization of Late Endosomal Membrane Domains* , 2002, The Journal of Biological Chemistry.