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Abstract
<p class="first" id="P1">About twenty years ago, the functional lipid raft model of
the plasma membrane was
published. It took into account decades of research showing that cellular membranes
are not just homogenous mixtures of lipids and proteins. Lateral anisotropy leads
to assembly of membrane domains with specific lipid and protein composition regulating
vesicular traffic, cell polarity, and cell signaling pathways in a plethora of biological
processes. However, what appeared to be a clearly defined entity of clustered raft
lipids and proteins became increasingly fluid over the years, and many of the fundamental
questions about biogenesis and structure of lipid rafts remained unanswered. Experimental
obstacles in visualizing lipids and their interactions hampered progress in understanding
just how big rafts are, where and when they are formed, and with which proteins raft
lipids interact. In recent years, we have begun to answer some of these questions
and sphingolipids may take center stage in re-defining the meaning and functional
significance of lipid rafts. In addition to the archetypical cholesterol-sphingomyelin
raft with liquid ordered (Lo) phase and the liquid-disordered (Ld) non-raft regions
of cellular membranes, a third type of microdomains termed ceramide-rich platforms
(CRPs) with gel-like structure has been identified. CRPs are “ceramide rafts” that
may offer some fresh view on the membrane mesostructure and answer several critical
questions for our understanding of lipid rafts.
</p>