ReviewMembrane mechanisms for signal transduction: The coupling of the meso-scale raft domains to membrane-skeleton-induced compartments and dynamic protein complexes
Highlights
► The plasma membrane exhibits the three-tiered meso-scale domain architecture. ► The first tier is actin membrane-skeleton-induced compartments (partitioning). ► The second tier consists of raft domains with enormously varied sizes and lifetimes. ► The third tier is made of dynamic protein complex domains. ► Raft domains co-exist and work cooperatively with the domains of other tiers.
Section snippets
Introduction: general strategies for functional organization of the plasma membrane (membrane mechanisms)
In recent years, our understanding of the plasma membrane has advanced far beyond the textbook model of Singer and Nicolson [1]. Such new knowledge should be applied to research for the mechanistic understanding of plasma membrane functions. However, cell and developmental biologists and biomedical researchers are only slowly grasping the critically important, new concepts regarding the molecular mechanisms and the dynamic structures in the plasma membrane.
In this review, we will summarize our
Hypothesis of the hierarchical three-tiered meso-scale domain architecture of the plasma membrane
As an initial effort for developing such a general, fundamental understanding of the membrane mechanisms, we propose the concept of the hierarchical three-tiered meso-scale (2–300 nm) domain architecture of the plasma membrane (Fig. 1). In this review, we hope to persuade the readers that we can obtain an excellent perspective of the functional mechanisms of the plasma membrane by using this concept of the hierarchical three-tiered meso-domain architecture of the plasma membrane, in which all
Co-existence of actin-induced membrane compartments and raft domains in a single plasma membrane
Surprisingly, quite a few researchers appear to consider the actin-induced membrane compartments and the raft domains as warring either-or concepts. However, we found no evidence showing that one of them exclusively exists in the plasma membrane. On the contrary, all of the available data indicate the co-existence of the actin-membrane-skeleton-induced membrane compartments and the raft domains in a single plasma membrane. Therefore, another main aim of this review is to convince the readers
New molecular mechanisms revealed by fast single-molecule imaging
Recent developments in single-molecule techniques that are applicable to studies of living cells have provided researchers the unprecedented ability to directly observe the movement, assembly, and even activation of individual molecules in the plasma membrane [2], [30], [31], [32], [33]. High-speed single-molecule imaging and tracking methods have turned out to be particularly useful. Video-rate imaging, with a frame rate of 30 frames per second, is generally used in our normal daily lives,
The first tier: membrane-skeleton-induced compartments (partitioning)
The partitioning of the plasma membrane by the actin-based membrane skeleton and its associated TM proteins is summarized in the following eight points in this review. Due to space limitations, fuller accounts of the membrane-skeleton-induced compartments are published elsewhere [34].
The second tier: meso-scale raft domains
The concept of raft domains is still being developed. However, it is becoming clear that for the proper development of the raft fields, two key features of the raft domains should clearly be understood. (1) The raft domain properties are distinctly different between before and after stimulation. Therefore, raft domains before and after stimulation should never be mixed in the discussion except for the cases where stimulation-induced changes of raft domains are considered. (2) Since raft domains
The third tier: dynamic protein complex domains
We consider three types of “dynamic protein complex domains”, as shown in Fig. 8 (3):
(3a) oligomers of membrane-anchored proteins and protein complexes based on them,
(3b) coat-protein-facilitated domains,
(3c) scaffolding-protein-induced protein complexes.
Increasingly more researchers have started considering that signal transduction is performed not only by the collision or interaction of two molecules, but also by the multimolecular assemblies in/on the plasma membrane. Such multimolecular
Conclusions
The plasma membrane amplifies and modulates the signal received from the outside world, multiplexes it with other signals, branches it into many cytoplasmic signaling pathways with varied signal levels, and spreads it two-dimensionally along the plasma membrane as well as three-dimensionally by endocytosis. Thus, the plasma membrane works like a network of many computers that is connected to enormous numbers of sensors and actuators. However, the analogy stops here. In the electronic circuit of
Acknowledgements
We thank all of the members of the Kusumi Lab for fruitful discussions and critical reading of this manuscript, and Mr. Kohji Kanemasa for preparing the figures. This work was supported in part by Grants-in-Aid for Scientific Research from the MEXT (AK, KGNS, and TKF) and by Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (KGNS). R.C. is a recipient of the Postdoctoral Fellowship for Foreign Researchers, awarded by the Japan Society for the
References (194)
- et al.
Lipid rafts and plasma membrane microorganization: insights from Ras
Trends Cell Biol
(2004) - et al.
Nanoscale organization of multiple GPI-anchored proteins in living cell membranes
Cell
(2004) - et al.
Nanoclusters of GPI-anchored proteins are formed by cortical actin-driven activity
Cell
(2008) - et al.
Segregation of GM1 and GM3 clusters in the cell membrane depends on the intact actin cytoskeleton
Biochim Biophys Acta Mol Cell Biol Lipids
(2009) - et al.
Single-molecule diffusion reveals similar mobility for the Lck, H-Ras, and K-Ras membrane anchors
Biophys J
(2006) - et al.
PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function
Cell
(2008) - et al.
A new paradigm for membrane-organizing and -shaping scaffolds
FEBS Lett
(2006) Imaging endocytic clathrin structures in living cells
Trends Cell Biol
(2009)- et al.
Subcellular membrane curvature mediated by the BAR domain superfamily proteins
Semin Cell Dev Biol
(2010) - et al.
Ultrafine membrane compartments for molecular diffusion as revealed by single molecule techniques
Biophys J
(2004)