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lipid rafts; detergent-insoluble glycolipid-rich domains (DIGs); glycolipid-enriched membranes (GEMs); low-density Triton-insoluble (LDTI) complexes
Cholesterol-rich microdomains in the exoplasmic leaflet of the membrane bilayer. Plasma membrane lipid rafts consist of clusters of about 20 proteins & ~3500 sphingolipid molecules. They are about 50 nm in diameter, but may aggregate into the um range by receptor activation or bivalent antibodies against raft- associated surface antigens. Lipid rafts may also occur in the GOLGI.
Constituents:
1) lipids
a) cholesterol
b) sphingolipids
- sphingomyelin
- gangliosides (i.e. GM1)
2) proteins
a) integral membrane proteins
- flotillins
- caveolin
- stomatins
- LAT/PAG
- MAL/BENE
- VIP36
b) glypiated proteins (exoplasmic face)
- Thy-1
- alkaline phosphatase
- folate receptor
c) cytoplasmic face (proteins modified with alphipatic groups)
- src family tyrosine kinases
- G-alpha protein
- endothelial NO synthase (eNOS, NOS-3)
- H-ras
d) scavenger receptors
- CD36
- SRBI
- RAGE
e) tyrosine kinase receptors
- EGF receptor
- PDGF receptor
- insulin receptor
f) endothelin receptor
g) neuronal lipid rafts [5]
- amyloid precursor protein (APP)*
- APP gamma-secretase
- BACE1
* substrate (APP#) & enzymes (APP gamma-secretase & BACE1) present in neuronal lipid rafts. beta-Peptide (dimers) may accumulate in neuronal lipid rafts in mouse-model for Alzheimer's disease. apoE & phosphorylated tau found associated with the lipid rafts after appearance of beta-peptide. [5]
# most APP is not within lipid rafts
Function:
1) vesicular trafficking
2) signal transduction
3) compartment for APP gamma-secretase
3) formation of caveolae
Related
advanced glycosylation end product [AGE] receptor (AGER, RAGE)
alkaline phosphatase
CD36; platelet glycoprotein 4; platelet glycoprotein IV; GPIV; glycoprotein IIIb; GPIIIB; leukocyte differentiation antigen CD36; PAS IV; PAS-4; platelet collagen receptor; fatty acid translocase; FAT; Thrombospondin receptor (GP3B, GP4)
CD90; thy-1 membrane glycoprotein; thy-1 antigen; CDw90 (THY1)
cholesterol
endothelin receptor
epidermal growth factor receptor; receptor tyrosine-protein kinase ErbB-1 (EGFR, ERBB1, HER1)
flotillin
folate receptor or folate-binding protein
G-protein
ganglioside
glypiated protein
H-ras proto-oncogene protein (Harvey ras, p21Hras, Ha-ras)
insulin receptor; IR; (INSR)
NO synthase-3 (endothelial NO synthase, NOS3, ENOS)
platelet-derived growth factor [PDGF] receptor
sphingomyelin
src proto-oncogene protein family
Specific
caveola
General
cellular membrane
References
- Galbiati et al, Cell 106:403, 2001
PMID: 11525727
- Simon & Toomre, Nature Reviews 1:31, 2000
PMID: 11413487
- Marx J. Science 294:1862, 2001
- Nebl T et al, JBC 277(45):43399 2002
PMID: 12202484
- Kawarabayashi T et al, J Neurosci 24(15):3801, 2004
PMID: 15084661