Biology Reference
In-Depth Information
membranes
[76]
. Therefore one would expect that raft proteins should exhibit a longer hydro-
phobic match surface than non-raft proteins. However, to date it has yet to be shown that
a protein's hydrophobic span length is related to its preferential location in rafts. The rough
surface associated with the membrane-spanning portion of an integral protein should exclude
trans-membrane proteins from
l
o
state raft lipids. Indeed, most trans-membrane proteins do
associate poorly with DRMs. However, rafts are known to accommodate a few characteristic
trans-membrane proteins. The question remains, what makes raft integral proteins different
from non-raft integral proteins and why are they concentrated in rafts?
There aremany reports where polyunsaturated fatty acyl chains including arachidonic acid
(20:4
6
5,8,11,14
) and docosahexaenoic acid (22:6
6
4.7.10.13.16.19
) have been found at significant
levels among raft lipids
[77]
. This seems contrary to the basic precept that rafts exist in the
tightly packed
l
o
state. Howdoes a raft accommodate a highly contorted polyunsaturated fatty
acid? To justify this contradiction it has been proposed for PI(4,5)P
2
, a common component of
rafts, that the
sn
-2 arachidonic chain fits into a groove on a protein's surfacewhile the saturated
stearic
sn
-1chain inserts into the bilayer
[78]
. The effect of cholesterol depletion on trans-
membrane signaling functions has become a cornerstone in defining rafts. Yet even this has
its problems. Cholesterol levels can affect membrane structure and function by ways that
are unrelated to raft structure. For example, Pike and Miller
[79]
have made a strong case
that cholesterol depletion affects both raft structure and signaling through PI(4,5)P
2
.
It is now clear that DRMs are not exactly the same as lipid rafts that are resident in the
plasma membrane
[75]
. The current lipid raft model is in flux and will continue to be adjusted
to match new experimental findings.
One Last Word on Rafts
The fundamental importance of the lipid raft model was to propose a type of domain that
could serve as a simple paradigm for general membrane structure/function. Unfortunately,
the original concept of a lipid raft has continued to evolve, becoming ever more complex to
where it is now hard to define exactly what a lipid raft is and is not. Raft dynamics is poorly
understood and fixed rules remain elusive. Listed below are some recently suggested lipid
raft characteristics:
Lipid Raft Characteristics
1.
Rafts are highly regulated and may occur only in response to stimulation.
2.
In unstimulated cells, rafts are very small and unstable
e
if they exist at all.
3.
Lipid rafts have a high affinity for ordered lipids.
4.
Plasma membrane lipid composition is maintained close to that required for phase
separation so that small changes in protein or lipid can have a large influence on
lipid rafts.
5.
Caveolins and flotillins probably organize rafts into specialized membrane
domains.
6.
Some raft proteins are linked to the actin cytoskeleton network.
7.
The myristate/palmitate motif on lipoproteins appears to be an especially efficient
raft-targeting signal.
