Dynamic ergosterol- and ceramide-rich domains in the peroxisomal membrane serve as an organizing platform for peroxisome fusion.
We describe unusual ergosterol- and ceramide-rich (ECR) domains in the membrane of yeast peroxisomes. Several key features of these detergent-resistant domains, including the nature of their sphingolipid constituent and its unusual distribution across the membrane bilayer, clearly distinguish them from well characterized detergent-insoluble lipid rafts in the plasma membrane. A distinct set of peroxisomal proteins, including two ATPases, Pex1p and Pex6p, as well as phosphoinositide- and GTP-binding proteins, transiently associates with the cytosolic face of ECR domains. All of these proteins are essential for the fusion of the immature peroxisomal vesicles P1 and P2, the earliest intermediates in a multistep pathway leading to the formation of mature, metabolically active peroxisomes. Peroxisome fusion depends on the lateral movement of Pex1p, Pex6p, and phosphatidylinositol-4,5-bisphosphate-binding proteins from ECR domains to a detergent-soluble portion of the membrane, followed by their release to the cytosol. Our data suggest a model for the multistep reorganization of the multicomponent peroxisome fusion machinery that transiently associates with ECR domains.
Boukh-Viner
Tatiana
T
Department of Biology, Concordia University, Montreal, Quebec H4B 1R6, Canada.
Guo
Tong
T
Alexandrian
Alex
A
Cerracchio
André
A
Gregg
Christopher
C
Haile
Sandra
S
Kyskan
Robert
R
Milijevic
Svetlana
S
Oren
Daniel
D
Solomon
Jonathan
J
Wong
Vivianne
V
Nicaud
Jean-Marc
JM
Rachubinski
Richard A
RA
English
Ann M
AM
Titorenko
Vladimir I
VI
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology; D004875:Ergosterol / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D008561:Membrane Fusion / Q000187:drug effects / Q000502:physiology*; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism; D025062:Yarrowia / Q000378:metabolism
D002518:Ceramides; D003902:Detergents; D005656:Fungal Proteins; D013107:Sphingolipids; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; C085187:PEX6 protein, Yarrowia lipolytica; D004875:Ergosterol
Mol Biol Cell. 2003 Feb;14(2):611-24
12589058
J Bacteriol. 1991 Mar;173(6):2026-34
2002005
Proc Natl Acad Sci U S A. 2003 May 13;100(10):5813-8
12724530
Nat Rev Mol Cell Biol. 2003 Jun;4(6):468-78
12778126
Rev Physiol Biochem Pharmacol. 2003;147:75-121
12687401
Nat Rev Immunol. 2003 Jul;3(7):557-68
12876558
J Cell Biol. 2003 Sep 29;162(7):1255-66
14504266
Cell. 2003 Nov 14;115(4):377-88
14622593
J Cell Sci. 2004 Feb 29;117(Pt 6):805-13
14963021
Traffic. 2004 Apr;5(4):231-40
15030564
Traffic. 2004 Apr;5(4):247-54
15030566
Traffic. 2004 Apr;5(4):255-64
15030567
Nat Rev Mol Cell Biol. 2004 Feb;5(2):110-20
15040444
Cell. 1992 Feb 7;68(3):533-44
1531449
Methods Enzymol. 1992;219:369-87
1488010
J Cell Biol. 1998 Jul 27;142(2):403-20
9679140
J Cell Biol. 2000 Jan 10;148(1):29-44
10629216
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3254-9
10716729
J Biol Chem. 2000 Jun 9;275(23):17221-4
10770957
J Cell Biol. 2000 Aug 21;150(4):881-6
10953011
Nat Cell Biol. 2000 Sep;2(9):582-92
10980698
Annu Rev Biochem. 2000;69:399-418
10966464
Trends Cell Biol. 2001 Jan;11(1):22-29
11146295
Nat Rev Mol Cell Biol. 2000 Oct;1(1):31-9
11413487
Nat Rev Mol Cell Biol. 2001 Jul;2(7):504-13
11433364
Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9471-3
11504934
J Biol Chem. 2001 Sep 7;276(36):33540-6
11432870
Annu Rev Cell Dev Biol. 2001;17:701-52
11687502
Annu Rev Cell Dev Biol. 2002;18:289-314
12142286
J Cell Biol. 2004 Jun 7;165(5):735-46
15173190
Cell. 2003 Feb 21;112(4):519-33
12600315